CAPPA: Consistent Analysis of Action Potential Parameters for Various Types of Cardiomyocytes

In recent years, human induced pluripotent stem cellderived cardiomyocytes (hiPSC-CMs) have become an emerging tool in cardiovascular research.However, due to the spontaneous electrical activity and diverse morphologies of hiPSC-CM action potentials (APs), manual extraction of AP parameters is time-consuming and depends on the operator's subjective judgment, which hampers reproducible, quantitative comparisons between various types of CMs.Here, we introduce a consistent, fast, reproducible and operator-independent algorithm, which extracts quantitative AP parameters from recordings of various CM types.Markers for the start of an AP, maximum upstroke velocity, peak potential and maximum diastolic potential (MDP) are derived automatically.The algorithm was tested on 501 AP recordings from hiPSC-CMs, 873 AP recordings from stimulated isolated native CMs, 133 AP recordings from HL-1 cells and 100 AP recordings from computational electrophysiological simulations.The markers placed by the algorithm were validated against manual expert inspection and were considered correct in over 99% of cases.This open source algorithm enables standardized, reproducible and operator-independent high-throughput analyses of diverse AP recordings, facilitating quantitative comparisons of electrophysiological properties in various types of CMs.