Assessment of persistent atrial fibrillation arrhythmogenesis in the right atrium using digital twins

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) therapies; however, in persistent AF (PsAF), characterized with fibrosis proliferation, its success is limited. Various extra-PVI strategies have also failed to improve outcome. Although PsAF entails inflammation-driven remodeling throughout the atria, the left atrium (LA) has been the main focus of ablative therapies. We hypothesized that the suboptimal outcomes of PsAF treatment are attributable to the arrhythmogenic role of the right atrium (RA).

Using personalized digital twins (DTs), an emergent technology recently shown promise in non-invasively characterizing PsAF arrhythmogenesis, we aimed to mechanistically ascertain the difference in PsAF arrhythmogenesis between LA and RA post-PVI.

From 61 patients with PsAF's late gadolinium enhancement magnetic resonance imaging, bi-atrial DTs incorporating fibrosis distribution were constructed. In each DT, following virtual PVI, PsAF arrhythmogenesis was assessed by identifying potential rotor-sustaining locations (LRs) following rapid pacing. Fibrotic and electrophysiological features of LRs were analyzed and compared between the LA and RA.

Of 46 DTs with qualified images, 169 LRs were identified outside the PVI lesions, with substantial LR presence in the RA (66%). Fibrosis fraction within RA-LRs was higher than within LA-LRs. Fibrosis density and entropy and endocardial voltages at RA-LRs were comparable to LA-LRs. Age was found to be the independent determinant of PsAF arrhythmogenesis in RA.

DT analysis demonstrated that the RA contributed equally to PsAF arrhythmogenesis after PVI and exhibited fibrotic and electrophysiological features comparable to those of the LA post-PVI. Controlling RA arrhythmogenesis may be essential for PsAF management.