First-Pass Isolation as an Independent Predictor of Atrial Fibrillation Recurrence After Cryoballoon Ablation in Patients with Persistent Atrial Fibrillation

<b>Background/Objectives</b>: Data on predictors of atrial fibrillation (AF) recurrence after cryoballoon pulmonary vein isolation (PVI) in persistent AF (PeAF) remain limited. We evaluated clinical, echocardiographic, and procedural parameters associated with recurrence. <b>Methods</b>: We retrospectively studied 192 PeAF patients who underwent cryoballoon PVI and had ≥6 months of follow-up. Recurrence was any atrial tachyarrhythmia > 30 s beyond a 3-month blanking period. Cox models assessed predictors, including number of veins with first-pass isolation (FPI), left atrial volume index (LAVI), hemoglobin, and prespecified covariates. <b>Results</b>: During a median follow-up of 670 days (interquartile range 425-944), recurrence occurred in 75 patients (39.1%). On multivariable analysis, reduced extent of FPI (<3 veins) independently predicted recurrence (HR 2.48, 95% CI 1.48-4.16; <i>p</i> = 0.001). In continuous analysis, each one-vein decrement in FPI was associated with a 58% higher hazard. Lower hemoglobin was also independently associated; each 1 g/dL decrease corresponded to a 29% higher hazard (HR 1.29, 95% CI 1.05-1.58; <i>p</i> = 0.015). Male sex showed approximately a twofold higher recurrence risk than female sex (HR 2.23, 95% CI 1.06-4.68; <i>p</i> = 0.034). In PeAF patients treated with cryoballoon PVI, intraprocedural FPI extent was a strong independent predictor, outperforming anatomical remodeling after adjustment. Achieving FPI in fewer than three pulmonary veins predicted higher recurrence. Hemoglobin provides an accessible systemic risk marker, while male sex identifies a higher-risk subgroup. <b>Conclusions</b>: In PeAF patients, the extent of FPI in cryoballoon PVI is a strong independent predictor of outcome, and maximizing the number of veins with FPI could be a pragmatic procedural goal.