Background Left atrial substrate may have mechanistic relevance for ablation of atrial fibrillation (AF). We sought to analyze the relationship between low‐voltage zones (LVZs), transition zones, and AF recurrence in patients undergoing pulmonary vein isolation. Methods and Results We conducted a prospective multicenter study on consecutive patients undergoing pulmonary vein isolation‐only approach. LVZs and transition zones (0.5–1 mV) were analyzed offline on high‐density electroanatomical maps collected before pulmonary vein isolation. Overall, 262 patients (61±11 years, 31% female) with paroxysmal (130 pts) or persistent (132 pts) AF were included. After 28 months of follow‐up, 73 (28%) patients experienced recurrence. An extension of more than 5% LVZ in paroxysmal AF and more than 15% in persistent AF was associated with recurrence (hazard ratio [HR], 4.4 [95% CI, 2.0–9.8], P <0.001 and HR, 1.9 [95% CI, 1.1–3.7], P =0.04, respectively). Significant association was found between LVZs and transition zones and between LVZs and left atrial volume index (LAVI) (both P <0.001). Thirty percent of patients had significantly increased LAVI without LVZs. Eight percent of patients had LVZs despite normal LAVI. Older age, female sex, oncological history, and increased AF recurrence characterized the latter subgroup. Conclusions In patients undergoing first pulmonary vein isolation, the impact of LVZs on outcomes occurs with lower burden in paroxysmal than persistent AF, suggesting that not all LVZs have equal prognostic implications. A proportional area of moderately decreased voltages accompanies LVZs, suggesting a continuous substrate instead of the dichotomous division of healthy or diseased tissue. LAVI generally correlates with LVZs, but a small subgroup of patients may present with disproportionate atrial remodeling, despite normal LAVI.

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