4.4 Impact of the AWT on AF drivers in lesser LGE areas
Recent computational studies of patient-specific atrial models, based on the reconstruction of fibrosis from LGE-MRI, have provided mechanistic insights into the role of fibrosis in the dynamics of electrical re-entrant drivers sustaining AF. Zahid et al. have demonstrated that AF was sustained by re-entrant drivers persisting in fibrosis border zones.3 We previously reported that the LGE properties in anchoring AF drivers predominantly consist of heterogenous LGE areas in persistent AF patients. However, AF drivers are also observed in lesser LGE areas.7 Roy et al. reported that the AWT gradients played an important role in anchoring AF drivers in the absence of fibrosis.8 In an optical mapping ex vivo study of perfused right atria from explanted diseased human hearts, activation delays between the endocardium and epicardium during atrial pacing were more prominent in areas with an increased wall thickness, transmural fiber orientation angle gradient, and interstitial fibrosis.17 Therefore, thicker parts of the LA could be the 3D rotational substrate perpetuating AF due to long activation delays between the endocardium and epicardium. However, those have not been validated in humans.
In our study, there was a significant difference in the proportion of MRs/MWs in the %NP between the lesser and heterogenous LGE areas. Handa et al. recently reported that the fibrosis pattern alters the mechanism of the fibrillatory organization and its persistence in Langendorff-perfused rat hearts. They demonstrated that meandering rotational activation was mainly found with less fibrosis and less gap junction uncoupling and it disorganized into multiple wavelets in the progression of atrial fibrosis and gap junction uncoupling.18 Therefore, we speculated that the NPAs in lesser LGE areas might have been mainly caused by a complex fiber orientation in the three-dimensionally large space between the endocardium and epicardium. This might facilitate long activation delays between the endocardium and epicardium, which result in a 3D rotational substrate perpetuating AF. To the best of our knowledge, this is the first human study focusing on the impact of the AWT in lesser LGE areas on AF drivers using LGE-MRI.