Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Myocytes, Cardiac*/metabolism ; Heart Failure*/physiopathology ; Arrhythmias, Cardiac*/physiopathology ; Arrhythmias, Cardiac*/etiology ; Action Potentials*; Humans ; Diastole/physiology ; Models, Cardiovascular ; Myocardial Contraction/physiology ; Computer Simulation ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism

Chronic heart failure is one of the most common reasons for hospitalization. Current risk stratification is based on ejection fraction, whereas many arrhythmic events occur in patients with relatively preserved ejection fraction. We aim to investigate the mechanistic link between proarrhythmic abnormalities, reduced contractility and diastolic dysfunction in heart failure, using electromechanical modelling and simulations of human failing cardiomyocytes. We constructed, calibrated and validated populations of human electromechanical models of failing cardiomyocytes, that were able to reproduce the prolonged action potential, reduced contractility and diastolic dysfunction as observed in human data, as well as increased propensity to proarrhythmic incidents such as early afterdepolarization and beat-to-beat alternans. Our simulation data reveal that proarrhythmic incidents tend to occur in failing myocytes with lower diastolic tension, rather than with lower contractility, due to the relative preserved SERCA and sodium calcium exchanger current. These results support the inclusion of end-diastolic volume to be potentially beneficial in the risk stratifications of heart failure patients.
(© 2024. The Author(s).)

Erratum in: Sci Rep. 2024 Aug 27;14(1):19921. doi: 10.1038/s41598-024-70961-y.. (PMID: 39198564)

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RE/13/1/30181 The Oxford BHF Centre of Research Excellence; icp013 PRACE-ICEI funding projects; R39207/CN063 Oxford-Bristol Myers Squibb Fellowship; NC/P001076/1 United Kingdom NC3RS_ National Centre for the Replacement, Refinement and Reduction of Animals in Research; NC/P001076/ 1 an NC3Rs Infrastructure for Impact Award; 214290/Z/18/Z Wellcome Trust (Wellcome); icp005 PRACE-ICEI funding projects; icp019 PRACE-ICEI funding projects; United Kingdom WT_ Wellcome Trust

Keywords: Arrhythmia; Contractility; Diastolic tension; Electromechanics; Heart failure; Modelling

EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)

Date Created: 20240729 Date Completed: 20240729 Latest Revision: 20250530

20250530

PMC11286957

10.1038/s41598-024-65249-0

39075069