Key result
At therapeutic concentrations, hydroxychloroquine increased action potential duration by 1.4% to 2.6% without affecting alternans thresholds, suggesting no significant atrial proarrhythmogenic effects.
Why the study?
Hydroxychloroquine is commonly used for autoimmune diseases and increases the risk of QT interval prolongation, prompting quantitative examination of its potential arrhythmogenic effects on atrial fibrillation.
Does hydroxychloroquine affect atrial electrophysiology and arrhythmogenesis in in silico wild-type and PITX2+/- atrial cardiomyocytes?
Does hydroxychloroquine affect atrial electrophysiology and arrhythmogenesis in in silico wild-type and PITX2+/- atrial cardiomyocytes?
In silico modeling suggests therapeutic concentrations of hydroxychloroquine do not have significant atrial arrhythmogenic effects, but supratherapeutic doses may increase AF risk, especially with concomitant PITX2 mutations.
Hydroxychloroquine (HCQ) is commonly used in the treatment of autoimmune diseases and increases the risk of QT interval prolongation. We quantitatively examined the potential atrial arrhythmogenic effects of HCQ on atrial fibrillation (AF) using a computational model of human atrial cardiomyocytes. We measured atrial electrophysiological markers after systematically varying HCQ concentrations. HCQ concentrations were positively correlated with the action potential duration (APD), resting membrane potential, refractory period, APD alternans threshold, and calcium transient alternans threshold (P<0.05). In contrast, HCQ concentrations were inversely correlated with the maximum upstroke velocity and calcium transient amplitude (P<0.05). When the therapeutic concentration (Cmax) of HCQ was applied, HCQ increased APD90 by 1.4% in normal sinus rhythm, 1.8% in wild-type AF, and 2.6% in PITX2+/- AF, but did not affect the alternans thresholds. The overall in silico results suggest no significant atrial arrhythmogenic effects of HCQ at Cmax, rather implying a potential antiarrhythmic role of low-dose HCQ in AF. However, at HCQ of 4-fold Cmax, a rapid pacing rate of 4 Hz could induce prominent APD alternans, particularly in the PITX2+/- AF model. Concomitant PITX2 mutations and HCQ treatments may increase the risk of AF, and this potential arrhythmogenic effect of HCQ should be further investigated.
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Jun-Seop Song (2022) studied Atrial Fibrillation. Hydroxychloroquine vs. Baseline (no hydroxychloroquine) was evaluated on Action potential duration (APD90) at therapeutic concentration (Cmax) (p=<0.05). At therapeutic concentrations, hydroxychloroquine increased action potential duration by 1.4% to 2.6% without affecting alternans thresholds, suggesting no significant atrial proarrhythmogenic effects.
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