Cardiac arrhythmias are a major cause of death and disability. A large number of experimental cell and animal models have been developed to study arrhythmogenic diseases. These models have provided important insights into the underlying arrhythmia mechanisms and translational options for their therapeutic management. This position paper from the ESC Working Group on Cardiac Cellular Electrophysiology provides an overview of (i) currently available in vitro, ex vivo, and in vivo electrophysiological research methodologies, (ii) the most commonly used experimental (cellular and animal) models for cardiac arrhythmias including relevant species differences, (iii) the use of human cardiac tissue, induced pluripotent stem cell (hiPSC)-derived and in silico models to study cardiac arrhythmias, and (iv) the availability, relevance, limitations, and opportunities of these cellular and animal models to recapitulate specific acquired and inherited arrhythmogenic diseases, including atrial fibrillation, heart failure, cardiomyopathy, myocarditis, sinus node, and conduction disorders and channelopathies. By promoting a better understanding of these models and their limitations, this position paper aims to improve the quality of basic research in cardiac electrophysiology, with the ultimate goal to facilitate the clinical translation and application of basic electrophysiological research findings on arrhythmia mechanisms and therapies.

Department of Biotechnology and Bioscience University of Milano Bicocca Milano Italy

Department of Cardiology CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands

Department of Cardiology University Hospital Birmingham NHS Trust Birmingham UK

Department of Cardiology University Hospital Heidelberg Heidelberg Germany; Heidelberg Center for Heart Rhythm Disorders University Hospital Heidelberg Heidelberg Germany

Department of Experimental Cardiology Amsterdam UMC location AMC Amsterdam The Netherlands

Department of Internal Medicine and Cardiology Charité Universitätsmedizin Berlin Campus Virchow Klinikum Berlin Germany

Department of Physiology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

DZHK Partner Site Berlin Germany

German Centre for Cardiovascular Research Partner Site Hamburg Kiel Lübeck Germany

German Centre for Cardiovascular Research Partner Site Heidelberg Mannheim Germany

Institut de Génomique Fonctionnelle Université de Montpellier CNRS INSERM Montpellier France

Institute for Experimental Cardiovascular Medicine University Freiburg Germany

Institute of Cardiovascular and Medical Sciences University of Glasgow UK

Institute of Cardiovascular Sciences University of Birmingham Birmingham UK

Institute of Experimental Cardiovascular Research University Medical Center Hamburg Eppendorf Hamburg Germany

Institute of Pharmacology West German Heart and Vascular Center University Duisburg Essen Essen Germany

Institute of Physiology University of Bern Bern Switzerland

National Institute of Optics and European Laboratory for Non Linear Spectroscopy Italy

Signaling and cardiovascular pathophysiology UMR S 1180 Inserm Université Paris Saclay 92296 Châtenay Malabry France

Translational Cardiology Department of Cardiology Inselspital Bern University Hospital Bern Switzerland

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Lessons on the non-linear path of medical progress and biological complexity from mouse models of the Brugada syndrome

Modeling sepsis, with a special focus on large animal models of porcine peritonitis and bacteremia