Treating Atrial Fibrillation in Horses with LC-MS

A recent study conducted by the Japan Racing Association, the Laboratory of Racing Chemistry (Utsunomiya, Japan), The Royal Veterinary College (London, United Kingdom), andthe Université de Toulouse (France) aimed to demonstrate the variability in plasma quinidine (QND) concentrations between healthy Thoroughbred horses and horses with atrial fibrillation (AF). The objective being to determine the range of therapeutic and toxic QND concentrations in Thoroughbred horses. This led to the proposal of an empirical dosing regimen that was both effective and minimizing the risk of adverse drug effects for different probability of target attainment (PTA). QND in the plasma was assayed using a liquid chromatography system connected to a mass spectrometer. A paper based on this study was published in Frontiers in Veterinary Science (1).

A common performance-limiting arrhythmia in Thoroughbred horses, it is important to convert AF to normal sinus rhythm to recover racing performance (2–5). While there are several treatments have been proposed for AF, including propafenone (6), flecainide (7,8), amiodarone (9), and electrical cardioversion (10,11), QND is the most popular pharmacological treatment for thoroughbred horses (12,13).

The authors summarized their study as confirming the large variability in QND plasma concentrations, which they state can be attributed to both the variability of plasma clearance and individual bioavailability. The researchers also simulated different dosing scenarios, including those recommended in previous literature, before proposing a dosing regimen that ensures that the largest population (PTA of 80%) would be able to reach the therapeutic window. However, they acknowledge that it is difficult to propose an empirical dosing regimen capable of completely separating the range of therapeutic concentrations from those associated with risk of serious adverse effects (target PTA of 90%), which they believe indicates that QND treatment in horses is a candidate for therapeutic drug monitoring. In this respect, they state that their study is an essential first step that needs to be completed to ensure that the intra-individual variability of QND disposition, unlike the inter-individual variability, is limited (in practice, less than 30%) to make such a plasma monitoring approach clinically useful (1).

However, the authors also acknowledge there is the problem of limited access to chromatography and spectrometry measurement equipment in veterinary clinics. To promote optimal TDM methods in equine hospitals, they believe that it will be necessary to determine the number of samples required for TDM, their optimal collection times, and the evaluation of the predictive value of this approach (1).

Herd of Thoroughbred mares. © Mark J. Barrett - stock.adobe.com

References

1. Kuroda, T.; Minamijima, Y.; Kinman, C. K.; Takahashi, Y.; Ebisuda, Y.; Inoue, K.; Ishikawa, H.; Mita, H.; Tamura, N.; Nukada, T.; Toutain, P. L.; Ohta, M. Rational Quinidine Dosage Regimen for Atrial Fibrillation in Thoroughbred Racehorses Based on Population Pharmacokinetics. Front Vet. Sci. 2024, 11, 1454342. DOI: 10.3389/fvets.2024.1454342

2. Ohmura, H.; Hiraga, A.; Takahashi, T.; Kai, M. Jones, J. H. Risk Factors for Atrial Fibrillation During Racing in Slow-Finishing Horses. J. Am. Vet. Med. Assoc. 2003, 223, 84–88. DOI: /10.2460/javma.2003.223.84

3. Holmes, J. R.; Henigan, M.; Williams, R. B.; Witherington, D. H. Paroxysmal Atrial Fibrillation in Racehorses. Equine Vet. J. 1986, 18, 37–42. DOI: 10.1111/j.2042-3306.1986.tb03533.x

4. Decloedt, A.; Van Steenkiste, G.; Vera, L.; Buhl, R.; van Loon, G. Atrial Fibrillation in Horses Part 1: Pathophysiology. Vet. J. 2020, 263, 105521. DOI: 10.1016/j.tvjl.2020.105521

5. Nath, L. C.; Elliott, A.; La Gerche, A. Weir, J.; Forbes, G.; Thomas, G, et al. Associations Between Postrace Atrial Fibrillation and Measures of Performance, Racing History and Airway Disease in Horses. J. Vet. Intern Med. 2023, 37, 2573–2583. DOI: 10.1111/jvim.16878

6. De Clercq, D.; van Loon, G.; Tavernier, R.; Verbesselt, R.; Deprez, P. Use of Propafenone for Conversion of Chronic Atrial Fibrillation in Horses. Am. J. Vet. Res. 2009, 70, 223–227. DOI: 10.2460/ajvr.70.2.223

7. Carstensen, H.; Hesselkilde, E. Z.; Fenner, M.; Loft-Andersen, A. V.; Flethøj, M.; Kanters, J. K. et al. Time-Dependent Antiarrhythmic Effects of Flecainide on Induced Atrial Fibrillation in Horses. J. Vet. Intern Med. 2018, 32, 1708–1717. DOI: 10.1111/jvim.15287

8. Haugaard, M. M.; Pehrson, S.; Carstensen, H.; Flethøj, M.; Hesselkilde, E. Z.; Praestegaard, K.F. et al. Antiarrhythmic and Electrophysiologic Effects of Flecainide on Acutely Induced Atrial Fibrillation in Healthy Horses. J. Vet. Intern Med. 2015,29, 339–347. DOI: 10.1111/jvim.12496

9. De Clercq, D.; van Loon, G.; Baert, K.; Tavernier, R.; Croubels, S.; De Backer, P. et al. Effects of an Adapted Intravenous Amiodarone Treatment Protocol in Horses with Atrial Fibrillation. Equine Vet. J. 2007, 39, 344–349. DOI: 10.2746/042516407X182811

10. McGurrin, M. K.; Physick-Sheard, P. W.; Kenney, D. G. Transvenous Electrical Cardioversion of Equine Atrial Fibrillation: Patient Factors and Clinical Results in 72 Treatment Episodes. J. Vet. Intern Med. 2008, 22, 609–615. DOI: 10.1111/j.1939-1676.2008.0081.x

11. McGurrin, M. K.; Physick-Sheard, P. W.; Kenney, D. G. How to Perform Transvenous Electrical Cardioversion in Horses with Atrial Fibrillation. J. Vet. Cardiol. 2005, 7, 109–119. DOI: 10.1016/j.jvc.2005.09.001

12. Premont, A.; Balthes, S.; Marr, C. M.; Jeevaratnam, K. Fundamentals of Arrhythmogenic Mechanisms and Treatment Strategies for Equine Atrial Fibrillation. Equine Vet. J. 2022, 54, 262–282. DOI: 10.1111/evj.13518

13. Decloedt, A.; Van Steenkiste, G.; Vera, L.; Buhl, R.; van Loon, G. Atrial Fibrillation in Horses Part 2: Diagnosis, Treatment and Prognosis. Vet J. 2021, 268, 105594. DOI: 10.1016/j.tvjl.2020.105594