Towards Mechanisms-driven Strategy for Persistent Atrial Fibrillation Ablation: Leveraging Digital Twins

Figures

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  Fig. 1.. Recent approaches to driver identification during atrial fibrillation mapping A. ExTRa mapping B. CARTOFINDER C. Spatiotemporal electrogram dispersion (STED).

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  Fig. 2.. Clinical workflow of digital twin application CT = computed tomography; EAM = electroanatomic map; LGE-MRI = late gadolinium enhancement magnetic resonance imaging.

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  Fig. 3.. In silico substrate ablation targeting LRs (top) AF initiation in substrates from different pacing sites at LIPV (upper row) and LSPV (lower row). White arrows indicate direction of propagation. (middle) substrate ablation targeting an LR. Pink dot indicates the phase singularity location and red circular dashed line indicates the outline of the confined region of the persistent phase singularities. (bottom) LR ablation achieved AF non-inducibility. Red dot indicates ablation lesions. AF = atrial fibrillation; LIPV = left inferior pulmonary vein; LR = location of reentry; LSPV = left superior pulmonary vein. Adapted from McDowell et al., PloS one, 2016.

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  Fig. 4.. Flowchart of clinical application of DT-based ablation (top) Bi-atrial DTs incorporating fibrosis distribution were constructed from MRI images. Following LR identification by burst pacing at 40 bi-atrial sites, LRs were virtually ablated. Testing arrhythmia non-inducibility after each LR ablation and ablating any newly emerging LRs were repeated until no arrhythmia was inducible in the DT. The final set of DT-derived lesions was imported into the CARTO system and targeted during the ablation procedure. (bottom) Sustained AF observed before ablation was terminated during LR ablation, and non-inducibility of any arrhythmia was confirmed after ablation. AF = atrial fibrillation; DT = digital twin; LR = location of reentry; MRI = magnetic resonance imaging; OPTIMA = optimal target identification via modeling of arrhythmogenesis approach. Adapted from Boyle et al., Nature biomedical engineering, 2019.

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  Fig. 5.. Discernment of contingent LRs from identified LRs in the DT A. (top) Three LRs were identified in the DT. (bottom) Among 3 LRs, two were LIRs that required ablation to achieve arrhythmia non-inducibility and one was an LCR that lost its rotor-attracting capabilities when another LR was eliminated. B. By discerning LCRs from all identified LRs, this new “selective” approach to substrate ablation reduced the number of target locations by 34% over the entire DT patient cohort, thereby mitigating unnecessary extensive ablation and heart damage. DT = digital twin; LCR = location of contingent reentry; LIR = location of reentry; LR = location of reentry. Adapted from Sakata et al., Nature Cardiovascular Research, 2024.

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  Fig. 6.. Preventing scar-related macroreentrant AT by MRA A. (top) SSA lesions mimicked contiguous overlapping lesions created by radiofrequency ablation with normal power, forming a transmural compound lesion. (bottom) MRA lesions consisted of 4 smaller lesions resulting in the lesions on the opposite atrial surface not being connected to each other, avoiding a large anatomic obstacle favorable to reentry formation. Light-blue area indicates the atrial wall and red area indicates ablated scar tissue. B. SSA lesion executed at an LR caused scar-related macroreentrant AT, i.e., iAT, around the SSA lesion (left), while MRA lesion executed at that LR resulted in the prevention of iAT (right). C. Compared with SSA, MRA significantly reduced the occurrence rate of iAT by 18% across all LRs identified in the patients’ DTs. AT = atrial tachycardia; DT = digital twin; iAT = post-ablation iatrogenic AT; LR = location of reentry; MRA = multiple reduced-strength ablation; SSA = single-region standard ablation. Adapted with permission from Sakata et al., JACC. Clinical electrophysiology, 2024.

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  Fig. 7.. Patient stratification benefitting from WA-PVI or PWI + PVI A. (left) IO-PVI. (bottom) WA-PVI. (right) PWI + PVI. Red lines indicate linear ablation lesions. B. (left) PWI addition eliminated more LA-LRs than WA-PVI (69% vs. 60%) in the DT cohort, and WA-PVI was also significantly more beneficial than IO-PVI (60% vs. 49%) in diminishing LA substrate arrhythmogenicity. (right) In 60% of all PsAF patients’ DTs, PVI greatly decreased LA substrate arrhythmogenicity without the need of wider lesions or additional PWI. C. Fibrosis assessment could be useful for properly stratifying patients benefitting from PWI or wider PVI. DT = digital twin; FE = fibrosis entropy; FF = fibrosis fraction; IO-PVI = individual ostial PVI; LA = left atrium; LAPW = LA posterior wall; LGE-MRI = late gadolinium enhancement magnetic resonance imaging; LR = location of reentry; PsAF = persistent atrial fibrillation; PVI = pulmonary vein isolation; PWI = LAPW isolation; PWI + PVI = LAPW isolation plus WA-PVI; WA-PVI = wide antral PVI. Adapted from Sakata et al., NPJ digital medicine, 2025.