The treatment of atrial fibrillation and other cardiac arrhythmias as a major cause of cardiovascular hospitalization has remained a challenge predominantly for patients with severely remodeled substrate. Individualized ablation strategies are extremely important both for pulmonary vein isolation and subsequent ablations. Current approaches to identifying arrhythmogenic regions rely on electrogram-based features such as activation time and voltage. Novel technologies now enable clinical assessment of the local impedance as tissue property. Previous studies demonstrated its use for ablation monitoring and indicated its potential to differentiate healthy substrate, scar, and pathological tissue. This study investigates the potential of local electrical impedance-based substrate mapping of the atria for human in-vivo data. The presented pipeline for impedance mapping particularly contains options for dealing with undesirable effects originating from cardiac motion, catheter motion, or proximity to other intracardiac devices. Bloodpool impedance was automatically determined as a patient-specific reference. Full-chamber, left atrial impedance maps were drawn up from interpolating the measured impedances to the atrial endocardium. Finally, the origin and magnitude of oscillations of the raw impedance recording were probed into. The most dominant reason for exclusion of impedance samples was the loss of endocardial contact. With median elevations above the bloodpool impedance between 29 and 46 Ω, the impedance within the pulmonary veins significantly exceeded the remaining atrial walls presenting median elevations above the bloodpool impedance between 16 and 20 Ω. Previous ablation lesions were distinguished from their surroundings by a significant drop in local impedance while the corresponding regions did not differ for the control group. The raw impedance was found to oscillate with median amplitudes between 6 and 17 Ω depending on the patient. Oscillations were traced back to an interplay of atrial, ventricular, and respiratory motion. In summary, local impedance measurements demonstrated their capability to distinguish pathological atrial tissue from physiological substrate. Methods to limit the influence of confounding factors that still hinder impedance mapping were presented. Measurements at different frequencies or the combination of multiple electrodes could lead to further improvement. The presented examples indicate that electrogram- and impedance-based substrate mapping have the potential to complement each other toward better patient outcomes in future.

Background: Electrical impedance measurements have become an accepted tool for monitoring intracardiac radio frequency ablation. Recently, the long-established generator impedance was joined by novel local impedance measurement capabilities with all electrical circuit terminals being accommodated within the catheter. Objective: This work aims at in silico quantification of distinct influencing factors that have remained challenges due to the lack of ground truth knowledge and the superposition of effects in clinical settings. Methods: We introduced a highly detailed in silico model of two local impedance enabled catheters, namely IntellaNav MiFi™ OI and IntellaNav Sta-blepoint™, embedded in a series of clinically relevant environments. Assigning material and frequency specific conductivities and subsequently calculating the spread of the electrical field with the finite element method yielded in silico local impedances. The in silico model was validated by comparison to in vitro measurements of standardized sodium chloride solutions. We then investigated the effect of the withdrawal of the catheter into the transseptal sheath, catheter-tissue interaction, insertion of the catheter into pulmonary veins, and catheter irrigation. Results: All simulated setups were in line with in vitro experiments and in human measurements and gave detailed insight into determinants of local impedance changes as well as the relation between values measured with two different devices. Conclusion: The in silico environment proved to be capable of resembling clinical scenarios and quantifying local impedance changes. Significance: The tool can assists the interpretation of measurements in humans and has the potential to support future catheter development.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974 Regions with pathologically altered substrate have been identified as potentially responsible for atrial fibrillation and atrial flutter maintenance. Also, real time feedback on lesion formation especially in those critical areas is a challenge. The LOCALIZE trial has shown significant value of the usage of the local impedance (LI) drop as a real time indicator during ablation for durable lesion formation. In these procedures, a decrease of 10-20% of the initial LI value is used as a marker of successful ablation. Also known is the fact that low electrode-tissue contact force is associated with ineffective lesion formation, whereas a high value can lead to an increased risk of steam pop. The IntellaNavSTABLEPOINT catheter offers both, LI and contact force, as a novel combined technique to characterize the process of lesion formation. Additionally, LI values are expected to distinguish between healthy and scar tissue independently from the atrial rhythm, which can improve the understanding of underlying substrate, even more, when corrected for an eventual lack of contact by combining it with contact force. This study aims to: (1) evaluate the relationship between contact force and LI; (2) characterise the contact force during local impedance mapping depending on the wall region of the left atrium (LA). Patients undergoing LA ablation with the STABLEPOINT catheter were included in this analysis. Contact force and LI data were recorded in four different healthy anatomical points in the LA, two in the anterior wall, and two in the posterior wall, using manually controlled contact force values between 0 g and the saturation point (70 g). When possible, additional points in scar regions were recorded. Data were exported and processed to correlate each LI measurement with the corresponding contact force. Due to the susceptibility of raw LI recordings to oscillations, moving average approach was considered. The clinical cohort comprised ten patients with a mean age of 61 years, one female. De-Novo ablations as well as redo procedures were included. Measurements at different contact force values yielded a non-linear relationship between contact force and LI. Median value of the difference between the moving average LI measurement and the LI bloodpool value were calculated at the anterior and posterior walls of the LA at contact force values from 5 to 40 g (5 g step size). Comparing the LI values at each segment, measurements differ significantly (Mann-Whitney U-test for unpaired samples) between the anterior and the posterior wall of the LA, with an ascending trend. Scar points showed a globally lower curve. Results from this preliminary study showed that LI and contact force are non-linearly dependent and it differs between anterior and posterior atrial walls, as well as between healthy and pathological substrate. Further investigations in a larger clinical cohort will analyse the LI variability to set an optimal contact force technique during LI mapping.

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