Atrial Myocytes From Patients With Paroxysmal Atrial Fibrillation Show A Higher Predisposition To Arrhythmogenic Action Potential Alternans

Background: Alternans, the periodic beat-to-beat alternation in electrical and calcium signaling of a cardiac myocyte stimulated at a fixed frequency is well documented to be proarrhythmic. Nonetheless, the involvement of alternans in the processes promoting paroxysmal atrial fibrillation (pAF) is unknown. As such, we set out to ascertain if alternans contribute to the arrhythmogenic mechanisms in pAF. Methods: Simultaneous action potentials (patch-clamp) and [Ca 2+ ] i (Fluo3) were recorded in right atrial myocytes obtained from patients with sinus rhythm (Ctl; n=16) and pAF (n=8). AP and CaT alternans were acquired and analyzed using a custom-written software. Results: AP duration was similar between pAF and Ctl groups over different pacing frequencies, exempting electrical remodeling in pAF. A higher incidence of CaT alternans (46% vs 18%; P =0.08) and AP alternans (82% vs 52%; P <0.05) was observed in myocytes from pAF patients compared with Ctl ( Figure A ). Additionally, the minimum frequency at which AP alternans was detected was significantly lower in pAF (2.4 ± 0.8 vs 4.6 ± 0.6 Hz; n/N=9/6 pAF vs 13/12 Ctl; P <0.05; Figure B ). However, the AP restitution was unchanged in Ctl and pAF myocytes ( Figure C ), thus suggesting CaT alternans as the primary driver of AP alternation ( Figure D ). Conclusion: Atrial myocytes from pAF patients exhibit a higher predisposition to cellular alternans that may alter excitation-propagation in the atria and contribute to the arrhythmogenic substrate in these patients.