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

Max Cumberland, Leto L. Riebel, Ashwin Roy, Christopher O'Shea, Andy Holmes, Chris Denning, Paulus Kirchhof, Blanca Rodriguez, Katja Gehmlich

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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.
Original languageEnglish
Article number806366
Number of pages23
JournalFrontiers in Physiology
Volume13
DOIs
Publication statusPublished - 7 Feb 2022

Bibliographical note

Funding Information:
This work was funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs; NC/T001747/1 to KG and MC). Work in KG’s laboratory is funded by the British Heart Foundation (BHF) (PG/19/45/34419 and FS/12/40/29712); the Medical Research Council (MR/ V009540/1); and the Wellcome Trust (201543/B/16/Z and 204846/Z/16/Z to UoB). LR is funded by a BBSRC PhD scholarship in collaboration with AstraZeneca (BB/V509395/1). BR is funded by a Wellcome Trust Senior Research Fellowship in Basic Biomedical Sciences (214290/Z/18/Z) and an NC3Rs Infrastructure for Impart Award (NC/P001076/1). AH is funded by the BHF Project grant (PG/17/30/32961) and a BHF Studentship (FS/PhD/20/29093). The Institute of Cardiovascular Sciences, University of Birmingham, has received an Accelerator Award by the British Heart Foundation (AA/18/2/34218). CO’S is funded by a Wellcome Trust (Sir Henry Wellcome Fellowship 221650/Z/20/Z). AR is funded by a BHF Accelerator (AA/18/2/34218). CD is funded by the British Heart Foundation (CRMR/21/290009, PG/21/10545) and the National Centre for the Replacement, Refinement, and Reduction of Animals in Research (35911–259146, NC/K000225/1, NC/S001808/1).

Publisher Copyright:
Copyright © 2022 Cumberland, Riebel, Roy, O’Shea, Holmes, Denning, Kirchhof, Rodriguez and Gehmlich.

Keywords

  • cardiac arrhythmias
  • heart failure
  • human induced pluripotent stem cells
  • in silico modelling
  • in vivo cardiac models
  • methods

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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