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Review
. 2022 Feb 7:13:806366.
doi: 10.3389/fphys.2022.806366. eCollection 2022.

Basic Research Approaches to Evaluate Cardiac Arrhythmia in Heart Failure and Beyond

Max J Cumberland  1 , Leto L Riebel  2 , Ashwin Roy  1 , Christopher O'Shea  1 , Andrew P Holmes  1   3 , Chris Denning  4 , Paulus Kirchhof  1   5 , Blanca Rodriguez  2 , Katja Gehmlich  1   6
Affiliations
Review

Basic Research Approaches to Evaluate Cardiac Arrhythmia in Heart Failure and Beyond

Max J Cumberland et al. Front Physiol. .

Abstract

Patients with heart failure often develop cardiac arrhythmias. The mechanisms and interrelations linking heart failure and arrhythmias are not fully understood. Historically, research into arrhythmias has been performed on affected individuals or in vivo (animal) models. The latter however is constrained by interspecies variation, demands to reduce animal experiments and cost. Recent developments in in vitro induced pluripotent stem cell technology and in silico modelling have expanded the number of models available for the evaluation of heart failure and arrhythmia. An agnostic approach, combining the modalities discussed here, has the potential to improve our understanding for appraising the pathology and interactions between heart failure and arrhythmia and can provide robust and validated outcomes in a variety of research settings. This review discusses the state of the art models, methodologies and techniques used in the evaluation of heart failure and arrhythmia and will highlight the benefits of using them in combination. Special consideration is paid to assessing the pivotal role calcium handling has in the development of heart failure and arrhythmia.

Keywords: cardiac arrhythmias; heart failure; human induced pluripotent stem cells; in silico modelling; in vivo cardiac models; methods.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
In vivo models used in cardiac arrhythmia and heart failure research. An outline of the animals used in arrhythmia and heart failure research, their electrophysiological similarities and differences in relation to humans, the advantages (green) and limitations (red) of their use and the techniques most commonly used in their evaluation. The size of the animal represents the prevalence of their use. Created with BioRender.com
Figure 2
Figure 2
In vivo models used in cardiac arrhythmia and heart failure research. An outline of the in vitro cell models used in arrhythmia and heart failure research, how they are derived (left), the format in which they can be used (middle right) and the techniques most commonly used in their evaluation (right). Complexity of the model used increases from bottom (primary cell suspension) to top (microfluidic heart on chip). Created with BioRender.com
Figure 3
Figure 3
The benefits of a “Team Science” approach in cardiac arrhythmia and heart failure research. Created with Biorender.com.
See this image and copyright information in PMC

References

    1. Adderley N. J., Ryan R., Nirantharakumar K., Marshall T. (2019). Prevalence and treatment of atrial fibrillation in UK general practice from 2000 to 2016. Heart 105, 27–33. doi: 10.1136/heartjnl-2018-312977, PMID: - DOI - PubMed
    1. Aguirre L. A., Alonso M. E., Badía-Careaga C., Rollán I., Arias C., Fernández-Miñán A., et al. (2015). Long-range regulatory interactions at the 4q25 atrial fibrillation risk locus involve PITX2c and ENPEP. BMC Biol. 13:26. doi: 10.1186/s12915-015-0138-0, PMID: - DOI - PMC - PubMed
    1. Ahuja P., Perriard E., Perriard J. C., Ehler E. (2004). Sequential myofibrillar breakdown accompanies mitotic division of mammalian cardiomyocytes. J. Cell Sci. 117, 3295–3306. doi: 10.1242/jcs.01159, PMID: - DOI - PubMed
    1. Alloui A., Zimmermann K., Mamet J., Duprat F., Noel J., Chemin J., et al. (2006). TREK-1, a K+ channel involved in polymodal pain perception. EMBO J. 25, 2368–2376. doi: 10.1038/sj.emboj.7601116, PMID: - DOI - PMC - PubMed
    1. Amano Y., Nishiguchi A., Matsusaki M., Iseoka H., Miyagawa S., Sawa Y., et al. (2016). Development of vascularised iPSC derived 3D-cardiomyocyte tissues by filtration layer-by-layer technique and their application for pharmaceutical assays. Acta Biomater. 33, 110–121. doi: 10.1016/j.actbio.2016.01.033, PMID: - DOI - PubMed

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