Instantaneous Amplitude and Frequency Modulations Detect the Footprint of Rotational Activity and Reveal Stable Driver Regions as Targets for Persistent Atrial Fibrillation Ablation.

Costly proprietary panoramic multielectrode (64-256) acquisition systems are being increasingly used together with conventional electroanatomical mapping systems for persistent atrial fibrillation (PersAF) ablation. However, such approaches target alleged drivers (rotational/focal) regardless of their activation frequency dynamics. To test the hypothesis that stable regions of higher than surrounding instantaneous frequency modulation (iFM) drive PersAF and determine whether rotational activity is specific for such regions. First, novel single-signal algorithms based on instantaneous amplitude modulation (iAM) and iFM to detect rotational-footprints without panoramic multielectrode acquisition systems were tested in 125 optical movies from 5 ex vivo Langendorff-perfused PersAF sheep hearts (sensitivity/specificity, 92.6/97.5%; accuracy, 2.5-mm) and in computer simulations. Then, 16 pigs underwent high-rate atrial pacing to develop PersAF. After a median (interquartile range [IQR]) of 4.4 (IQR, 2.5-9.9) months of high-rate atrial pacing followed by 4.1 (IQR, 2.7-5.4) months of self-sustained PersAF, pigs underwent in vivo high-density electroanatomical atrial mapping (4920 [IQR, 4435-5855] 8-second unipolar signals per map). The first 4 out of 16 pigs were used to adapt ex vivo optical proccessing of iFM/iAM to in vivo electrical signals. In the remaining 12 out of 16 pigs, regions of higher than surrounding average iFM were considered leading-drivers. Two leading-driver + rotational-footprint maps were generated 2.6 (IQR, 2.4-2.9) hours apart to test leading-driver spatiotemporal stability and guide ablation. Leading-driver regions (2.5 [IQR, 2.0-4.0] regions/map) exactly colocalized (95.7%) in the 2 maps, and their ablation terminated PersAF in 92.3% of procedures (radiofrequency until termination, 16.9 [IQR, 9.2-35.8] minutes; until nonsustainability, 20.4 [IQR, 12.8-44.0] minutes). Rotational-footprints were found at every leading-driver region, albeit most (76.8% [IQR, 70.5%-83.6%]) were located outside. Finally, the translational ability of this approach was tested in 3 PersAF redo patients. Both rotational-footprints and spatiotemporally stable leading-driver regions can be located using iFM/iAM algorithms without panoramic multielectrode acquisition systems. In pigs, ablation of leading-driver regions usually terminates PersAF and prevents its sustainability. Rotational activations are sensitive but not specific to such regions. Single-signal iFM/iAM algorithms could be integrated into conventional electroanatomical mapping systems to improve driver detection accuracy and reduce the cost of patient-tailored/mechanistic approaches.