Voltage-Guided Ablation for Atrial Fibrillation -- Current Insights and Future Directions

The prevalence of atrial fibrillation (AF) is forecasted to increase manifold, emphasizing the need for efficacious treatments. Pulmonary vein isolation (PVI) to eliminate ectopic triggers is now established as a fundamental component of the invasive treatment of AF, however its efficacy in persistent AF remains suboptimal. The atrial myocardium undergoes adverse fibrotic remodeling as AF progresses, favoring arrhythmia initiation and maintenance. Reductions in left atrial bipolar voltage have been suggested to identify regions of such pathological remodeling, and represent novel targets for ablation to target the arrhythmogenic substrate. Early observational studies targeting these low voltage areas (LVA) have been encouraging, however results from more recent randomized trials are more mixed. Importantly, there is significant heterogeneity in the techniques for identifying LVAs and the strategies for ablation. In reality, the atrial arrhythmogenic substrate is multi-faceted rather than being limited to fibrosis and there remains uncertainty as to how accurately LVAs represent regions of fibrosis. Additionally, bipolar voltage is influenced by numerous physiological and biophysical factors. The present review summarizes the current evidence for LVA ablation in AF. We then analyze the components of the atrial arrhythmic substrate, its relationship to LVAs and the limitations in LVA assessment. Finally we discuss novel techniques for delineating the atrial substrate.