Pinpointing atrial fibrillation drivers by informed sequential endocardial mapping in the presence and absence of fibrosis: an in-silico study

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work is part of Personalize AF. This project received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974. This work was also supported by the Swiss National Supercomputing Centre (CSCS), project s1074. BACKGROUND: We recently developed a novel technique to localize spatially stable atrial fibrillation (AF) drivers using the combined information from sequential endocardial mapping recordings. The robustness of this technique to localize drivers in the presence of complex substrate with a high degree of fibrosis and with unstable and meandering drivers is not known. PURPOSE: To evaluate the effect of spatial instability of drivers and high AF substrate complexity caused by atrial fibrosis on the performance of the recently developed technique for AF driver localisation using sequential endocardial mapping. METHODS: We used a previously validated volumetric 3D atrial model to simulate AF initiated by incremental pacing. Two sets of simulation were generated, with no structural changes (n=7), and with severe remodelling (n=11), implemented as patches of endomysial fibrosis covering 70% of the atria. Simulated endocardial unipolar electrograms were generated sequentially in a 4x4 electrode grid (3 mm spacing, 2.5 s) starting from 20 uniformly spaced positions in the atria. The subsequent catheter positions were determined by analysing the propagation direction in the grid. If the measured activity was repetitive, the dominant direction of propagation was determined, and the catheter was repositioned 10 mm upstream within the same atrium. Otherwise, the catheter was moved 5 mm in a random direction. This procedure continued until either 1) a driver (re-entry or radial spread of activations) was detected directly at the recorded region by evaluating the corresponding propagation patterns, or 2) the previous catheter positions defined an enclosed region in the atrium, encircling the AF driver. The performance of the algorithm was compared between the two remodelling stages with respect to number of steps required to locate a driver, and to the distance to the closest driver. RESULTS: In the simulations with fibrosis more drivers were present than in the simulations without fibrosis (4 [2, 6] vs. 3 [2; 4] simultaneous reentries, p < 0.001). Drivers were spatially unstable and meandered substantially through the atrium. The performance of the algorithm to localize the drivers was similar in both groups. The tracking procedures located a driver after 6 [IQR: 4; 9] vs. 5 [3; 8] steps (p<0.01). The algorithm localized the driver correctly in 72.8% vs. 78.2% (p = 0.30) of the cases and the final distances to a driver were 7.87 [5.88; 11.04] mm and 7.78 [5.55, 11.35] mm (p=0.95), respectively. More drivers were detected by encircling them with sequential catheter positions in the cases without remodelling (62.6% vs. 40.9%, p<0.001). CONCLUSION: Guiding mapping catheters by functional aspects of AF and combining sequential recordings may increase the efficiency and accuracy of mapping procedures. The developed algorithm successfully localizes AF drivers even in complex substrates for AF. [Figure: see text] [Figure: see text]