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ATRIAL FIBRILLATION

Atrial fibrillation induces functional remodelling of the left ventricle

Nature Reviews Cardiology volume 19, page 285 (2022)Cite this article

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Clinical data indicate that atrial fibrillation (AF) can cause left ventricular (LV) dysfunction and heart failure (HF). However, whereas the pathogenesis of AF has been broadly studied in the atria, the effects of AF on LV function are poorly understood. A new study now demonstrates that AF alone, in the absence of tachycardia, causes functional remodelling of the left ventricle via impairment of excitation–contraction coupling of ventricular cardiomyocytes, which is mediated by reduced systolic Ca2+ release and increased levels of oxidative stress. “We unravel the chicken-and-egg principle of AF and HF, showing that the arrhythmic ventricular excitation caused by AF leads to a structural and functional disturbance of ventricular function,” highlight lead investigators Steffen Pabel and Samuel Sossalla.

Given that the clinical characteristics of the patients might have influenced the observed phenotypes, the researchers performed in vitro experiments of AF stimulation (using arrhythmic or rhythmic pacing at 60 bpm) in human isolated primary cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). These in vitro models confirmed the detrimental phenotypes associated with AF observed in clinical samples. After 24 h of AF simulation, human LV cardiomyocytes from non-failing hearts showed impaired Ca2+ transient amplitude. In iPSC-CMs, 7 days of AF simulation led to a depression in systolic Ca2+ transient amplitude, as well as decreased Ca2+ load and increased diastolic Ca2+ leak from the sarcoplasmic reticulum. AF simulation also induced increases in cytosolic Na+ concentration and the late Na+ current, which led to prolongation of the action potential duration.

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  • Dridi, H. et al. Intracellular calcium leak in heart failure and atrial fibrillation: a unifying mechanism and therapeutic target. Nat. Rev. Cardiol. 17, 732–747 (2020)

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Irene Fernández-Ruiz

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  1. Irene Fernández-Ruiz
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Correspondence to Irene Fernández-Ruiz.

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Fernández-Ruiz, I. Atrial fibrillation induces functional remodelling of the left ventricle. Nat Rev Cardiol 19, 285 (2022). https://doi.org/10.1038/s41569-022-00689-7

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  • DOI: https://doi.org/10.1038/s41569-022-00689-7

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