Recent studies strongly suggest that the majority of atrial fibrillation (AF) patients with diagnosed or subclinical cardiac diseases have established or even pre-existing fibrotic structural remodeling, which may lead to conduction abnormalities and reentrant activity that sustain AF. As conventional treatments fail to treat AF in far too many cases, an urgent need exists to identify specific structural arrhythmogenic fibrosis patterns, which may maintain AF, in order to identify effective ablation targets for AF treatment. However, the existing challenge is to define what exact structural remodeling within the complex 3D human atrial wall is arrhythmogenic, as well as linking arrhythmogenic fibrosis to an underlying mechanism of AF maintenance in the clinical setting. This review is focused on the role of 3D fibrosis architecture in the mechanisms of AF maintenance revealed by submillimeter, high-resolution ex-vivo imaging modalities directly of human atria, as well as from in-silico 3D computational techniques that can be able to overcome in-vivo clinical limitations. The systematic integration of functional and structural imaging ex-vivo may inform the necessary integration of electrode and structural mapping in-vivo. A holistic view of AF driver mechanisms may begin to identify the defining characteristics or "fingerprints" of reentrant AF drivers, such as 3D fibrotic architecture, in order to design optimal patient-specific ablation strategies.
Keywords: atrial fibrillation; computer model; fibrosis; human atria; optical mapping; reentrant driver.