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Introduction: Although pulmonary vein (PV) isolation (PVI) is very effective in paroxysmal atrial fibrillation (AF), in patients (pts) with persistent AF, PVI often is not sufficient. Many studies suggested that low voltage zones (LVZs) outside of the PV might be involved in the complex mechanisms perpetuating AF. However ablation strategies involving substrate modification (SM) did not show additional benefits in persistent AF pts. Those studies were performed before the introduction of contact force technology, and the most likely explanation for these results could be the inability to achieve effective transmural lesions and continuous linear ablation. Hypothesis: We hypothesized that the use of contact force technology would improve ablation efficacy. Therefore, we analyzed the long-term outcome after two different ablation strategies in pts with persistent AF depending on whether there was evidence of LVZs in the left atrium or not. Methods: The presence of LVZs were defined as sites of >3 adjacent low-voltage points 400g/s. Ablation was performed in a temperature-controlled fashion with energy of 30W except at the posterior wall (20-25W). Results: 121 consecutive pts with persistent AF (46 female, median age 66 [59-72] years, mean duration of AF 16 [7-73] months, CT derived LA volume index 66 [56-75]ml/m2) were included: pts without LVZs underwent PVI alone (n = 74), in pts with LVZs, PVI + SM (n = 47) was performed (mitral Isthmus line in 2, supero-septal line in 39, and roof line in 47; bidirectional block was achieved in 100%, 97%, and 100%, respectively). After a median follow-up of 13 [6-21] months, 86% of pts without and 78% with substrate were in sinus rhythm, mainly without antiarrhythmic drugs (89% PVI only, 84% PVI + SM). Conclusions: In patients with persistent AF without LVZs, PVI alone leads to excellent 2-year freedom from AF. In pts with LVZs, additional substrate modification with CF sensing technology is associated with improved success rates compared to previous studies.