Time‐dependent antiarrhythmic effects of flecainide on induced atrial fibrillation in horses

Abstract

BackgroundPharmacological treatment of atrial fibrillation (AF) in horses can be challenging because of low efficacy and adverse effects. Flecainide has been tested with variable efficacy.ObjectiveTo test whether the efficacy of flecainide is dependent on AF duration.AnimalsNine Standardbred mares.MethodsFactorial study design. All horses were instrumented with a pacemaker and assigned to a control or an AF group. On day 0, all horses were in sinus rhythm and received 2 mg/kg flecainide IV. Atrial fibrillation subsequently was induced in the AF group by pacemaker stimulation. On days 3, 9, 27, and 55, flecainide was administered to all horses, regardless of heart rhythm.ResultsAll horses in AF cardioverted to sinus rhythm on days 3 and 9. On day 27, 5/6 horses cardioverted, whereas only 2/6 cardioverted on day 55. The time from the start of flecainide infusion to cardioversion (range, 3–185 min, log transformed) showed linear correlation with the cumulative duration of AF (r 2 = .80, P < .0001). Flecainide induced abnormal QRS complexes in 4/6 AF horses and 1/3 controls. A positive correlation was found between heart rate before flecainide infusion and number of abnormal QRS complexes (0.14, P < .05). One horse suffered from cardiac arrest and died after flecainide infusion.Conclusions and Clinical ImportanceFlecainide is effective for cardioversion of short‐term induced AF, but the effect decreases with AF duration. Controlling heart rate may minimize adverse effects caused by flecainide, but the drug should be used with great caution.

Effect of selective IK,ACh inhibition by XAF‐1407 in an equine model of tachypacing‐induced persistent atrial fibrillation

“…This hypothesis further supported by the observed increase in AFR with sustained AF over the 29 days is indicating progression of atrial electrical remodelling and corresponding to a decrease in the cardioversion rate in this study. Similar results have previously been reported for other AADs such as flecainide (Carstensen et al, 2018).…”

“…The equine model used in the present study has been validated in different experimental settings of AF (Carstensen et al, 2018; Haugaard, Hesselkilde, et al, 2015; Haugaard, Pehrson, et al, 2015; Hesselkilde et al, 2019). Even though tachypacing‐induced AF models in general might lack the exact substrate “lone AF” originates from man, choosing an animal species naturally developing lone AF, as the horse (Van Loon et al, 2002), might be of value in the development of AADs.…”

“…The cardioversion success rate with vernakalant was reported to be 55% in tachypaced goats with AF for 11 days (Van Hunnik et al, 2016) and 0% in pigs tachypaced for 18 ± 3 days (Diness et al, 2017). Flecainide treatment of tachypaced horses revealed a cardioversion rate of 33% after 55 days and displayed serious life‐threatening cardiac adverse effects (Carstensen et al, 2018).…”

“…As recently described in more detail (Carstensen et al, 2018), all 12 horses were implanted with either dual‐ ( n = 8) or single‐chamber ( n = 3) ICDs (Maximo® II CRT‐D D284TRK, Maximo® II DR D284DRG, Concerto® C174AWK, Maximo® II VR D284VRC; Medtronic Danmark A/S, Copenhagen, Denmark). Bipolar pacing leads (Tendril™ STS Pacing Leads, 100 cm; St. Judes Medical Denmark A/S, Glostrup, Denmark) were implanted into the right atrium under electrophysiological guidance enabling rapid atrial tachypacing with 600 bpm per 100 ms, using custom‐made pacing software (HRP 2.0; Medtronic Danmark A/S, Copenhagen, Denmark).…”

“…This study aimed to investigate the efficacy of I K,ACh inhibition by examining the anti‐arrhythmic and electrophysiological properties of the novel putatively potent and highly specific I K,ACh inhibitor, XAF‐1407, in an equine, atrial‐tachypacing‐induced model of persistent AF (Carstensen et al, 2018; Hesselkilde et al, 2019). This animal AF model reproduces important features of human AF and, furthermore, horses spontaneously develop AF both with and without underlying structural heart disease (Reef et al, 2014).…”