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.