Joe B Hakim1, Michael J Murphy1, Natalia A Trayanova1, Patrick M Boyle1,2. 1. Institute for Computational Medicine and Department of Biomedical Engineering, Johns Hopkins University, 3400 N. Charles St, 208 Hackerman Hall, Baltimore, MD, USA. 2. Department of Bioengineering, University of Washington, N310H Foege, Box 355061, Seattle WA, USA.
Abstract
AIMS: Efforts to improve ablation success rates in persistent atrial fibrillation (AF) patients by targeting re-entrant driver (RD) sites have been hindered by weak mechanistic understanding regarding emergent RDs localization following initial fibrotic substrate modification. This study aimed to systematically assess arrhythmia dynamics after virtual ablation of RD sites in computational models. METHODS AND RESULTS: Simulations were conducted in 12 patient-specific atrial models reconstructed from pre-procedure late gadolinium-enhanced magnetic resonance imaging scans. In a previous study involving these same models, we comprehensively characterized pre-ablation RDs in simulations conducted with either 'average human AF'-based electrophysiology (i.e. EPavg) or ±10% action potential duration or conduction velocity (i.e. EPvar). Re-entrant drivers seen under the EPavg condition were virtually ablated and the AF initiation protocol was re-applied. Twenty-one emergent RDs were observed in 9/12 atrial models (1.75 ± 1.35 emergent RDs per model); these dynamically localized to boundary regions between fibrotic and non-fibrotic tissue. Most emergent RD locations (15/21, 71.4%) were within 0.1 cm of sites where RDs were seen pre-ablation in simulations under EPvar conditions. Importantly, this suggests that the level of uncertainty in our models' ability to predict patient-specific ablation targets can be substantially mitigated by running additional simulations that include virtual ablation of RDs. In 7/12 atrial models, at least one episode of macro-reentry around ablation lesion(s) was observed. CONCLUSION: Arrhythmia episodes after virtual RD ablation are perpetuated by both emergent RDs and by macro-reentrant circuits formed around lesions. Custom-tailoring of ablation procedures based on models should take steps to mitigate these sources of AF recurrence.
AIMS: Efforts to improve ablation success rates in persistent atrial fibrillation (AF) patients by targeting re-entrant driver (RD) sites have been hindered by weak mechanistic understanding regarding emergent RDs localization following initial fibrotic substrate modification. This study aimed to systematically assess arrhythmia dynamics after virtual ablation of RD sites in computational models. METHODS AND RESULTS: Simulations were conducted in 12 patient-specific atrial models reconstructed from pre-procedure late gadolinium-enhanced magnetic resonance imaging scans. In a previous study involving these same models, we comprehensively characterized pre-ablation RDs in simulations conducted with either 'average human AF'-based electrophysiology (i.e. EPavg) or ±10% action potential duration or conduction velocity (i.e. EPvar). Re-entrant drivers seen under the EPavg condition were virtually ablated and the AF initiation protocol was re-applied. Twenty-one emergent RDs were observed in 9/12 atrial models (1.75 ± 1.35 emergent RDs per model); these dynamically localized to boundary regions between fibrotic and non-fibrotic tissue. Most emergent RD locations (15/21, 71.4%) were within 0.1 cm of sites where RDs were seen pre-ablation in simulations under EPvar conditions. Importantly, this suggests that the level of uncertainty in our models' ability to predict patient-specific ablation targets can be substantially mitigated by running additional simulations that include virtual ablation of RDs. In 7/12 atrial models, at least one episode of macro-reentry around ablation lesion(s) was observed. CONCLUSION: Arrhythmia episodes after virtual RD ablation are perpetuated by both emergent RDs and by macro-reentrant circuits formed around lesions. Custom-tailoring of ablation procedures based on models should take steps to mitigate these sources of AF recurrence.
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