Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes
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 abnor...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Research
2024
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| _version_ | 1811140334283915264 |
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| author | Zhou, X Levesque, P Chaudhary, K Davis, M Rodriguez, B |
| author_facet | Zhou, X Levesque, P Chaudhary, K Davis, M Rodriguez, B |
| author_sort | Zhou, X |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-09-25T04:20:20Z |
| format | Journal article |
| id | oxford-uuid:4ec8b569-d7d6-413f-b072-1c6940c29ea9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:20:20Z |
| publishDate | 2024 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:4ec8b569-d7d6-413f-b072-1c6940c29ea92024-08-07T19:33:41ZLower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4ec8b569-d7d6-413f-b072-1c6940c29ea9EnglishJisc Publications RouterNature Research2024Zhou, XLevesque, PChaudhary, KDavis, MRodriguez, BChronic 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. |
| spellingShingle | Zhou, X Levesque, P Chaudhary, K Davis, M Rodriguez, B Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes |
| title | Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes |
| title_full | Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes |
| title_fullStr | Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes |
| title_full_unstemmed | Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes |
| title_short | Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes |
| title_sort | lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes |
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