| 1. |
- Buhl, Rikke, et al.
(författare)
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Atrial fibrillatory rate as predictor of recurrence of atrial fibrillation in horses treated medically or with electrical cardioversion
- 2022
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Ingår i: Equine Veterinary Journal. - : Wiley. - 0425-1644 .- 2042-3306. ; 54:6, s. 1013-1022
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recurrence rate of atrial fibrillation (AF) in horses after cardioversion to sinus rhythm (SR) is relatively high. Atrial fibrillatory rate (AFR) derived from surface ECG is considered a biomarker for electrical remodelling and could potentially be used for the prediction of successful AF cardioversion and AF recurrence. Objectives: Evaluate if AFR was associated with successful treatment and could predict AF recurrence in horses. Study design: Retrospective multicentre study. Methods: Electrocardiograms (ECG) from horses with persistent AF admitted for cardioversion with either medical treatment (quinidine) or transvenous electrical cardioversion (TVEC) were included. Bipolar surface ECG recordings were analysed by spatiotemporal cancellation of QRST complexes and calculation of AFR from the remaining atrial signal. Kaplan-Meier survival curve and Cox regression analyses were performed to assess the relationship between AFR and the risk of AF recurrence. Results: Of the 195 horses included, 74 received quinidine treatment and 121 were treated with TVEC. Ten horses did not cardiovert to SR after quinidine treatment and AFR was higher in these, compared with the horses that successfully cardioverted to SR (median [interquartile range]), (383 [367-422] vs 351 [332-389] fibrillations per minute (fpm), P <.01). Within the first 180 days following AF cardioversion, 12% of the quinidine and 34% of TVEC horses had AF recurrence. For the horses successfully cardioverted with TVEC, AFR above 380 fpm was significantly associated with AF recurrence (hazard ratio = 2.4, 95% confidence interval 1.2-4.8, P =.01). Main limitations: The treatment groups were different and not randomly allocated, therefore the two treatments cannot be compared. Medical records and the follow-up strategy varied between the centres. Conclusions: High AFR is associated with failure of quinidine cardioversion and AF recurrence after successful TVEC. As a noninvasive marker that can be retrieved from surface ECG, AFR can be clinically useful in predicting the probability of responding to quinidine treatment as well as maintaining SR after electrical cardioversion.
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| 2. |
- Carstensen, Helena, et al.
(författare)
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Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation
- 2019
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Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1045-3873 .- 1540-8167. ; 30:4, s. 596-606
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The atrial fibrillatory rate is a potential biomarker in the study of antiarrhythmic drug effects on atrial fibrillation (AF). The purpose of this study was to evaluate whether dose-dependent changes in the atrial fibrillatory rate can be monitored on surface electrocardiography (ECG) following treatment with dofetilide, ranolazine, and a combination of the two in an acute model of AF in horses. Methods and Results: Eight horses were subjected to pacing-induced AF on 4 separate days. Saline (control), dofetilide, ranolazine, or a combination of dofetilide and ranolazine was administered in four incremental doses. Atrial fibrillatory activity was extracted from surface ECGs using spatiotemporal QRST cancellation. The mean atrial fibrillatory rate before drug infusion was 297 ± 27 fpm. Dofetilide reduced the atrial fibrillatory rate following the infusion of low doses (0.89 µg/kg, P < 0.05) and within 5 minutes preceding cardioversion (P < 0.05). Cardioversion with ranolazine was preceded by a reduction in the atrial fibrillatory rate in the last minute (P < 0.05). The combination of drugs reduced the atrial fibrillatory rate in a similar manner to dofetilide used alone. A trend toward a lower atrial fibrillatory rate before drug infusion was found among horses cardioverting on low doses of the drugs. Conclusion: The atrial fibrillatory rate derived from surface ECGs showed a difference in the mode of action on AF between dofetilide and ranolazine. Dofetilide reduced the atrial fibrillatory rate, whereas ranolazine displayed a cardioverting mechanism that was distinct from a slowing of the fibrillatory process.
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| 3. |
- Fenner, Merle Friederike, et al.
(författare)
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Effect of selective IK,ACh inhibition by XAF-1407 in an equine model of tachypacing-induced persistent atrial fibrillation
- 2020
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 177:16, s. 3778-3794
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF. Experimental Approach: The pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug-induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction. Key Results: XAF-1407 potently and selectively inhibited Kir3.1/3.4 and Kir3.4/3.4, underlying the IK,ACh current. XAF-1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (~20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened atrioventricular-nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia. Conclusion and Implications: XAF-1407 efficiently cardioverted sustained tachypacing-induced AF of short duration in horses without notable side effects. This supports IK,ACh inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.
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| 4. |
- Hesselkilde, Eva Z., et al.
(författare)
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Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation
- 2017
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported. Aim: The aim was to study characteristics of induced AF and its modification by flecainide. Methods: The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal. Results: At AF onset, AFR was 295±52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269±36 fpm in the control group (ns), and 364±26 fpm in the horses with spontaneous persistent AF (P<0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269±36 fpm to a plateau of 313±14 fpm before decreasing to 288±28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P<0.05). Conclusion: AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.
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| 5. |
- Hesselkilde, Eva Zander, et al.
(författare)
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Longitudinal study of electrical, functional and structural remodelling in an equine model of atrial fibrillation
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model. Method: Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrillatory rate (AFR), changes in electrocardiographic and echocardiographic variables and response to medical treatment (flecainide 2 mg/kg) were recorded over a period of 2 months. At the end of the study, changes in ion channel expression and fibrosis were measured and compared between the two groups. Results: AFR increased from 299 ± 33 fibrillations per minute (fpm) to 376 ± 12 fpm (p < 0.05) and atrial function (active left atrial fractional area change) decreased significantly during the study (p < 0.05). No changes were observed in heart rate or ventricular function. The AF group had more atrial fibrosis compared to the control group (p < 0.05). No differences in ion channel expression were observed. Conclusion: Horses with induced AF show signs of atrial remodelling that are similar to humans and other animal models.
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| 6. |
- Van Steenkiste, Glenn, et al.
(författare)
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Relationship between atrial fibrillatory rate based on analysis of a modified base-apex surface electrocardiogram analysis and the results of transvenous electrical cardioversion in horses with spontaneous atrial fibrillation
- 2021
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Ingår i: Journal of Veterinary Cardiology. - : Elsevier BV. - 1760-2734. ; 34, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the atrial fibrillatory rate (AFR) derived from a local right atrial intracardiac recording (RA-FR) and from a single-lead surface electrocardiogram (ECG) during atrial fibrillation (AF) and to evaluate the correlation with transvenous electrical cardioversion (TVEC) threshold (in Joules), number of shocks and cardioversion success rate in horses. Animals: ECGs and clinical records of horses with AF treated by TVEC. Horses were included if a simultaneous recording of the right atrial intracardiac electrogram and a modified base-apex ECG were available. Materials and methods: Clinical records of horses with AF treated by TVEC were reviewed. Three-minute long episodes of simultaneous electrograms and surface ECG during AF were selected for analysis and compared using Bland-Altman analysis. The mean RA-FR was measured from the deflections on the intracardiac electrogram, while the AFR was extracted from the surface ECG using spatiotemporal QRS and T-wave cancellation. Results: Seventy-three horses satisfied the inclusion criteria. The mean difference between RA-FR and AFR was −13 fibrillations per minute (fpm), the 95% limits of agreement were between −66 and 40 fpm, and there was a moderate (ρ = 0.65) correlation between RA-FR and AFR (p < 0.001). Neither RA-FR nor AFR appeared to influence the TVEC cardioversion threshold or the number of TVEC shocks applied. Conclusions: The AFR may allow non-invasive long-term monitoring of AF dynamics. Neither RA-FR nor AFR could be used to predict the minimal defibrillation threshold for TVEC.
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