The Fibrotic Substrate in Persistent Atrial Fibrillation Patients: Comparison Between Predictions From Computational Modeling and Measurements From Focal Impulse and Rotor Mapping

Abstract

Focal impulse and rotor mapping (FIRM) involves intracardiac detection and catheter ablation of re-entrant drivers (RDs), some of which may contribute to arrhythmia perpetuation in persistent atrial fibrillation (PsAF). Patient-specific computational models derived from late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) has the potential to non-invasively identify all areas of the fibrotic substrate where RDs could potentially be sustained, including locations where RDs may not manifest during mapped AF episodes. The objective of this study was to carry out multi-modal assessment of the arrhythmogenic propensity of the fibrotic substrate in PsAF patients by comparing locations of RD-harboring regions found in simulations and detected by FIRM (RDsim and RDFIRM) and analyze implications for ablation strategies predicated on targeting RDs. For 11 PsAF patients who underwent pre-procedure LGE-MRI and FIRM-guided ablation, we retrospectively simulated AF in individualized atrial models, with geometry and fibrosis distribution reconstructed from pre-ablation LGE-MRI scans, and identified RDsim sites. Regions harboring RDsim and RDFIRM were compared. RDsim were found in 38 atrial regions (median [inter-quartile range (IQR)] = 4 [3; 4] per model). RDFIRM were identified and subsequently ablated in 24 atrial regions (2 [1; 3] per patient), which was significantly fewer than the number of RDsim-harboring regions in corresponding models (p < 0.05). Computational modeling predicted RDsim in 20 of 24 (83%) atrial regions identified as RDFIRM-harboring during clinical mapping. In a large number of cases, we uncovered RDsim-harboring regions in which RDFIRM were never observed (18/22 regions that differed between the two modalities; 82%); we termed such cases “latent” RDsim sites. During follow-up (230 [180; 326] days), AF recurrence occurred in 7/11 (64%) individuals. Interestingly, latent RDsim sites were observed in all seven computational models corresponding to patients who experienced recurrent AF (2 [2; 2] per patient); in contrast, latent RDsim sites were only discovered in two of four patients who were free from AF during follow-up (0.5 [0; 1.5] per patient; p < 0.05 vs. patients with AF recurrence). We conclude that substrate-based ablation based on computational modeling could improve outcomes.

Identifying locations of re-entrant drivers from patient-specific distribution of fibrosis in the left atrium

“…These computational model predictions have been validated by a recent clinical study that linked the patient-specific LGE areas with locations of RDs recoded using electrocardiography [18]. Moreover, recent computational modelling studies by Boyle et al [19,20] have illustrated correlations between the locations of RDs predicted by patient-specific atrial models and the respective locations found with electrocardiographic imaging (ECGI) and focal impulse rotor modulation (FIRM). In addition to shedding light into the role of fibrosis in the RD dynamics, these studies pave the way to the identification of patient-specific RDs locations from image-based 3D atrial models.…”

“…To facilitate future clinical application, it needs to be further developed and clinically validated using EAM techniques such as FIRM or ECGI, which allow for identifying patient-specific RD locations. Indeed, these tools have been used by previous computational studies investigating RD locations by Boyle et al [19,20] to validate their findings and show a fair correlation between model predictions and clinical findings. Moreover, our workflow can be extended to incorporate further patient-specific details, such as atrial fibre orientation and electrophysiological heterogeneity.…”

Computational Modeling Identifies Embolic Stroke of Undetermined Source Patients with Potential Arrhythmic Substrate

“…These changes represented the effect of elevated transforming growth factor-β1, a key component of the fibrogenic signaling pathway. As in previous studies [5,15,16], tissue-scale effects of interstitial fibrosis and gap junction remodeling were represented by reducing overall conductivity and exaggerating the anisotropy ratio (σL:σT) from 5:1 to 8:1 (σL = 0.17708 S m −1 ; σT = 0.022135 S m −1 ).…”

Characterization of the human myocardium by optical coherence tomography

“…Diffusion‐tensor MRI has been demonstrated for imaging of fiber orientation in both the atria and ventricles . Delayed enhancement MRI and CT can be used for myocardial infarction and fibrosis imaging, which is useful for making accurate diagnoses, predicting outcomes after therapy and treatment planning. MRI and CT have also been used to image adipose in cardiac tissue .…”