Impact of Effective Refractory Period Personalization on Arrhythmia Vulnerability in Patient-Specific Atrial Computer Models

Background and Aims: The effective refractory period is one of the main electrophysiological properties governing arrhythmia maintenance, yet effective refractory period personalisation is rarely performed when creating patient-specific computer models of the atria to inform clinical decision-making. The aim of this study is to evaluate the impact of incorporating clinical effective refractory period measurements when creating in silico personalised models on arrhythmia vulnerability. Methods: Clinical effective refractory period measurements were obtained in seven patients from multiple locations in the atria. The atrial geometries from the electroanatomical mapping system were used to generate personalised anatomical atrial models. To reproduce patient-specific refractory period measurements, the Courtemanche cellular model was gradually reparameterised from control conditions to a setup representing atrial fibrillation-induced remodelling. Four different modelling approaches were compared: homogeneous (A), heterogeneous (B), regional (C), and continuous (D) distribution of effective refractory period. The first two configurations were non-personalised based on literature data, the latter two were personalised based on patient measurements. We evaluated the effect of each modelling approach by quantifying arrhythmia vulnerability and tachycardia cycle length. We performed a sensitivity analysis to assess the influence of effective refractory period measurement uncertainty on arrhythmia vulnerability. Results: The mean vulnerability was 3.4±4.0 %, 7.7±3.4 %, 9.0±5.1 %, 7.0±3.6 % for scenarios A to D, respectively. The mean tachycardia cycle length was 167.1±12.6ms, 158.4±27.5ms, 265.2±39.9ms, and 285.9±77.3ms for scenarios A to D, respectively. Incorporating perturbations to the measured effective refractory period in the range of 2, 5, 10 and 20ms, had an impact on the vulnerability of the model of 5.8±2.7 %, 6.1±3.5 %, 6.9±3.7 %, 5.2±3.5 %, respectively. Conclusion: Increased dispersion of the effective refractory period had a greater effect on reentry dynamics than on mean vulnerability values. The incorporation of personalised effective refractory period in the form of gradients had a greater impact on vulnerability than had a homogeneously reduced effective refractory period. Effective refractory period measurement uncertainty up to 20ms slightly influences arrhythmia vulnerability. Electrophysiological personalisation of atrial in silico models appears essential and warrants confirmation in larger cohorts. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project has received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974. This work was supported by the Leibniz ScienceCampus "Digital Transformation of Research" with funds from the programme "Strategic Networking in the Leibniz Association". The authors acknowledge support by the state of Baden-Wuerttemberg through bwHPC. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee of Staedtisches Klinikum Karlsruhe gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at https://doi.org/10.5281/zenodo.10726677