BACKGROUND: The wide area circumferential ablation (WACA) approach to atrial fibrillation is thought to result in \'substrate modification\' perhaps related to autonomic denervation. We examined this prospectively by comparing WACA and segmental pulmonary vein isolation (PVI) using noninvasive surrogate markers. METHODS: Heart rate variability (HRV) and signal averaged P wave (SAPW) data were derived from high-resolution (HR) recordings (\'SpiderView\' ELA Medical) made in sinus rhythm immediately before and 24 hours after ablation. RESULTS: Forty patients recruited (20 WACA; 20 PVI); cohorts were comparable. WACA caused marked SAPW change: P wave duration (PWD) (149[4.6] ms to 160[5.9] ms; P = 0.003), root mean square (RMS) (4.4[0.4]microV to 2.8[0.4]; P = 0.001) and energy content (30-150 Hz; 20.4 [3.6]microV(2)/s to 13.7[2.4]; P = 0.001). No significant change was seen after PVI. Heart rate increased after WACA and PVI (61.4 to 73.5 [P = 0.001]; 69.5 to 75.0 [P = 0.07], respectively). HRV was significantly influenced after WACA: low frequency power (LF) 5.7(0.4) to 3.6(0.4); P = 0.001), high-frequency power (HF) 4.6(0.4)-3.4(0.3); P = 0.024, and after PVI: LF 5.4(0.3) to 4.3(0.3); P = 0.024. HF: 4.4(0.4) to 3.0(0.4); P = 0.018). CONCLUSIONS: HR recordings exhibit change in HRV after WACA and PVI. Marked change in both HRV and SAPW is observed after WACA. SAPW variables provide a measure of atrial substrate change after WACA unrelated to autonomic denervation.