ForCEPSS—A framework for cardiac electrophysiology simulations standardization

Background and Objective: Simulation of cardiac electrophysiology (CEP) is an important research tool that is increasingly being adopted in industrial and clinical applications. Typical workflows for CEP simulation consist of a sequence of processing stages starting with building an anatomical model and then calibrating its electrophysiological properties to match observable data. While the calibration stages are common and generalizable, most CEP studies re-implement these steps in complex and highly variable workflows. This lack of standardization renders the execution of computational CEP studies in an efficient, robust, and reproducible manner a significant challenge. Here, we propose ForCEPSS as an efficient and robust, yet flexible, software framework for standardizing CEP simulation studies. Methods and Results: Key processing stages of CEP simulation studies are identified and implemented in a standardized workflow that builds on openCARP11https://opencarp.org/. Plank et al. (2021) and the Python-based carputils22https://git.opencarp.org/openCARP/carputils. framework. Stages include (i) the definition and initialization of action potential phenotypes, (ii) the tissue scale calibration of conduction properties, (iii) the functional initialization to approximate a limit cycle corresponding to the dynamic reference state according to an experimental protocol, and, (iv) the execution of the CEP study where the electrophysiological response to a perturbation of the limit cycle is probed. As an exemplar application, we employ ForCEPSS to prepare a CEP study according to the Virtual Arrhythmia Risk Prediction protocol used for investigating the arrhythmogenic risk of developing infarct-related ventricular tachycardia (VT) in ischemic cardiomyopathy patients. We demonstrate that ForCEPSS enables a fully automated execution of all stages of this complex protocol. Conclusion: ForCEPSS offers a novel comprehensive, standardized, and automated CEP simulation workflow. The high degree of automation accelerates the execution of CEP simulation studies, reduces errors, improves robustness, and makes CEP studies reproducible. Verification of simulation studies within the CEP modeling community is thus possible. As such, ForCEPSS makes an important contribution towards increasing transparency, standardization, and reproducibility of in silico CEP experiments.