Atrial Fibrillation (AF) is the most common arrhythmia in adults, especially in the elderly, with the increased incidence of stroke being a major complication that increases morbidity and mortality. The occurrence of AF is often accompanied by heart failure (HF). AF and HF are also known to have the bidirectional relationship that AF worsens HF and HF promotes AF. HF can induce atrial remodelling, including electrical remodelling, atrial fibrosis, stretch and dilatation, and oxidative stress, in which many factors are associated with arrhythmogenic atrial alternans. HF-induced atrial remodelling varies during various stages and complications of HF, but possible mechanisms underlying their pro-susceptibility to alternans have not been completely elucidated. In this study, we investigated the effects of HF-induced atrial remodelling with prolonged action potential duration (APD) and decreased cell-to-cell coupling on susceptibility to atrial alternans. Simulation results showed that HF-induced an increase in sarcoplasmic reticulum Ca2+-ATPase (SERCA) Ca2+ reuptake caused by increased phospholamban phosphorylation and a decrease in transient outward K+ current played significant roles in the genesis of Ca2+ transient alternans and action potential alternans at the single-cell level. The HF-induced decline of cell-to-cell coupling and APD prolongation promoted the genesis of spatially discordant alternans in atrial tissue. This provides insights into how HF facilitates atrial arrhythmia in relation to atrial alternans.
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