Post-ablation atrial arrhythmogenic channels predict atrial fibrillation recurrence - iatrogenic substrate revisited
Authors: Regany-Closa M , Pellicer B , Invers-Rubio E , Prat S , Guichard J B , Guasch E , Porta-Sanchez A , Tolosana J M , Arbelo E , Brugada J , Roca-Luque I , Mont L , Althoff T F 
Published: May 2024

Abstract

Background
Fibrosis is a hallmark of atrial fibrillation (AF) arrhythmogenic substrate, and the extent of atrial fibrosis, as determined by late gadolinium enhancement (LGE)-MRI, predicts AF recurrence after ablation. However, ablation fundamentally alters the individual composition of fibrotic tissue, and inhomogeneous ablation lesions may constitute an arrhythmogenic substrate themselves. From ventricular arrhythmias (VA) we know that it is not the extent of scar tissue that determines arrhythmogenicity, but rather the scar-pervading channels of surviving tissue with residual conduction.

Purpose
To investigate post-ablation arrhythmogenic substrate in terms of atrial scar channels using LGE-MRI.

Methods
Patients with PVI-only AF ablation were included. All patients received a systematic 12-months follow-up and an LGE-MRI 3 months post-ablation. Scar channels were defined as corridors of borderzone tissue (residual conduction), protected by dense scar. Channels were automatically identified using a software algorithm that has been extensively validated in the ventricle and was now adapted for the atrium.
To differentiate healthy tissue, borderzone and dense scar, LGE was quantified based on the signal intensity ratios of each voxel relative to the blood pool. Signal intensity ratio thresholds defining dense scar and borderzone, were then empirically tested to enhance the predictive value of the identified channels. The algorithm was then applied to an independent validation cohort using the empirically determined thresholds.

Results
150 patients were included. 10 different combinations of signal intensity ratio thresholds defining borderzone tissue and dense scar were empirically tested regarding the prediction of potentially arrhythmogenic channels in 50 patients (derivation cohort). For each of the threshold combinations, the number of predicted channels was linked to 12-months arrhythmia-free survival using logistic regression. The computed channels best predicted 12-months arrhythmia recurrence, when based on signal intensity ratios of 1.1-1.32 (borderzone) and &gt;1.32 (dense scar).
This threshold combination was then validated in an independent cohort of 100 patients. Patients with scar channels had significantly lower arrhythmia-free survival than those without (55% vs. 88%, p=0.016, Fig. 1). The number of detected scar channels was predictive of 12-months arrythmia recurrence (OR 4.9; p=0.012) – independent of other factors like LA diameter, AF type or the extent of native atrial fibrosis (pre-ablation LGE-MRI). Of note, the number of gaps in the PV-encircling lesions was not predictive of AF recurrence.

Conclusions
LGE-MRI-detected post-ablation scar channels predict recurrent AF after PVI and may be a surrogate of iatrogenic substrate. In light of large-area ablations with PFA and other single-shot devices fueling a trend towards more and more extensive lesions, the concept of iatrogenic arrhythmogenic substrate may have to be reconsidered.