HCN4 and atrial fibrillation: In normal rats, chronic ivabradine administration induced a significant increase in atrial HCN4 mRNA expression levels (Scridon et al., 2021), suggesting that If blockade may exert not anti-, but rather proarrhythmic effects over the long term, as also indicated by the modest, yet significant increase in AF rates recorded in the clinical studies that evaluated ivabradine (Martin et al., 2014; Cammarano et al., 2016).