Arrhythpy: an automated tool to quantify and classify arrhythmias in Ca2+ transients of iPSC-cardiomyocytes

Arrhythmias constitute an intricate and clinically significant phenomenon of great importance in various research areas. Calcium (Ca2+) homeostasis plays a pivotal role in forming rhythmic contractions in the heart, and its dysregulation has emerged as a critical component in the development of arrh...

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Hauptverfasser: Ajmail, Karim (VerfasserIn) , Brand, Charlotte (VerfasserIn) , Borchert, Thomas (VerfasserIn) , Meder, Benjamin (VerfasserIn) , Rebs, Sabine (VerfasserIn) , Streckfuss-Bomeke, Katrin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: November 2025
In: American journal of physiology. Heart and circulatory physiology
Year: 2025, Jahrgang: 329, Heft: 5, Pages: H1110-H1125
ISSN:1522-1539
DOI:10.1152/ajpheart.00414.2025
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1152/ajpheart.00414.2025
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Verfasserangaben:Karim Ajmail, Charlotte Brand, Thomas Borchert, Benjamin Meder, Sabine Rebs, and Katrin Streckfuss-Bomeke
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Zusammenfassung:Arrhythmias constitute an intricate and clinically significant phenomenon of great importance in various research areas. Calcium (Ca2+) homeostasis plays a pivotal role in forming rhythmic contractions in the heart, and its dysregulation has emerged as a critical component in the development of arrhythmias. However, the quantification of arrhythmias has been limited to indirect measurements via Ca2+ sparks, electrophysiological parameters, or manual classification, which can lead to human bias. We aimed to develop an analysis platform that automatically analyzes arrhythmias in human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Here, we present Arrhythpy, a robust and automated open-source program that quantifies and classifies confocal microscopy-based Fluo-4 Ca2+ transients to generate a measure of arrhythmia. In contrast to other automated and semiautomated analysis tools, which measure established parameters such as time-to-peak, Arrhythpy directly analyzes the degree of arrhythmia in a Ca2+ transient. We demonstrate its utility in monitoring Ca2+ transient-based arrhythmias in atrial and ventricular iPSC-CMs from healthy individuals and patients with cardiac disease, including dilated cardiomyopathy (DCM) and Takotsubo syndrome (TTS). Arrhythpy analysis of iPSC-CMs of patients with TTS recapitulated TTS phenotypes, including atrial arrhythmia that could be normalized with beta-blocker treatment. The program's adaptable framework enables the analysis of arrhythmic patterns in various cell types using periodic dye-based line scan measurement techniques, applicable to both single cells and layered cultures.
Beschreibung:Im Text sind "2" und "+" hochgestellt
Zuerst veröffentlicht: September 15, 2025
Gesehen am 27.02.2026
Beschreibung:Online Resource
ISSN:1522-1539
DOI:10.1152/ajpheart.00414.2025