Multimodal Characterization of the Atrial Substrate - Risks and Rewards of Electrogram and Impedance Mapping

The treatment of atrial rhythm disorders such as atrial fibrillation has remained a major challenge predominantly for patients with severely remodeled substrate. Individualized ablation strategies beyond pulmonary vein isolation in combination with real-time assess- ment of ablation lesion formation have been striven for insistently. Current approaches for identifying arrhythmogenic regions predominantly rely on electrogram-based features such as activation time and voltage or electrogram fractionation as a surrogate for tissue pathology. Despite bending every effort, large-scale clinical trials have yielded ambiguous results on the efficacy of various substrate mapping approaches without significant improvement of patient outcomes.
This work focuses on enhancing the understanding of electrogram features and local impedance measurements in the atria towards the extraction of clinically relevant and predic- tive substrate characteristics.
Features were extracted from intra-atrial electrograms with particular reference to the un- derlying excitation patterns to address morphological alterations caused by structural and functional changes. ... mehrThe noise level of unipolar electrograms was estimated and reduced by tailored filtering to enhance unipolar signal quality. Electrogram features exhibited nar- row distributions for healthy substrate across patients while a wide range was observed for pathologically altered excitation.
Additionally, local impedance was investigated as a novel parameter and mapping modality. Having been introduced to the medical device market recently for monitoring ablative lesion formation, initial clinical experiences with local impedance-enabled catheters lack comple- mentary systematic investigations. Confounding factors and the potential for application as a tool for substrate mapping need elucidation. This work pursued a trimodal approach combining in human, in vitro, and in silico experiments to quantitatively understand the effect of distinct ambient conditions on the measured local impedance. Forward simulations of the spread of the electrical field with a finite element approach as well as the application of inverse solution methods to reconstruct tissue conductivity were implemented in silico. Adequate preprocessing steps were developed for measurements in human to eliminate artefacts automatically. Two clinical studies on local impedance as an indicator for ablation lesion formation and on local impedance based substrate mapping were conducted. Local impedance recordings identified both previously ablated and native scar areas irrespective of local excitation. A highly detailed in silico environment for local impedance measurements was validated with in vitro recordings and provided quantitative insights into the influence of changes in clinically relevant scenarios. Inverse reconstruction of relative tissue conductivity yielded promising results in silico.
This work demonstrates that local impedance mapping shows great potential to comple- ment electrogram-based substrate mapping. A validated in silico environment for local impedance measurements can facilitate and optimize the development of next generation local impedance-enabled catheters. Conduction velocity, electrogram features, and recon- structed tissue conductivity suggest to be promising candidates for enhancing future clinical mapping systems.