Background <p>Fibrillatory wave amplitude (fWA) on 12-lead ECG predicts the outcome of ablation in atrial fibrillation (AF). We hypothesized that changes in fWA following wide circumferential isolation of pulmonary veins (WPVI) in persistent AF (peAF) is a better predictor of ablation outcome compared to baseline fWA.</p> Methods <p>Eighty-nine patients (sustained peAF 7 ± 7&#xa0;months) underwent a first-time WPVI. Sixty-second ECG signals devoid of QRST waves were recorded at baseline and at the end of the WPVI (endWPVI). fWA for each ECG lead and mean fWA (meanfWA) across the 12-lead ECG were computed. Patients with recurrence after the index WPVI underwent a redo to ensure complete PVI. The primary endpoint was long-term AF freedom OFF antiarrhythmics drugs (AADs) after one or two WPVI (SUCCESS group). The FAILURE group was defined as AF recurrence post-redo.</p> Results <p>Over a mean follow-up of 35 ± 10&#xa0;months, freedom from AF OFF AADs was achieved in 61% (SUCCESS group), while 29% had AF recurrence after redo WPVI (FAILURE group). The SUCCESS group showed significantly higher fWA values in ECG leads V₁, V₄, and V₅ at baseline (<i>p</i> &lt; 0.05), as well as in leads III, aVL, aVF, and V₄, and in meanfWA at endWPVI (<i>p</i> &lt; 0.05) compared to the FAILURE group. A baseline mean fWA ≥ 0.044&#xa0;mV or a decrease in mean fWA ≤ 11% following WPVI predicted long-term sinus rhythm restoration with a sensitivity of 81% and a specificity of 69% (<i>p</i> &lt; 0.05).</p> Conclusion <p>Low fWA values and a significant reduction in fWA following WPVI are associated with a high risk of AF recurrence in patients with peAF.</p> Graphical Abstract <p>Fibrillatory wave amplitude changes after WPVI can predict long-term sinus rhythm maintenance.</p> <p></p>