A 19-year-old 555-kg (1,221-lb) warmblood gelding was evaluated because of poor performance and an irregular heart rhythm. The gelding was used as a jumper and had exercise intolerance of 1 week's duration. On evaluation, cardiac auscultation revealed a high heart rate (60 beats/min) with an irregularly irregular rhythm. No heart murmurs were detected via auscultation. The quality of the mandibular arterial pulses was considered normal. Irregular jugular venous pulsation was evident in the distal third of the jugular groove. Results of a CBC and serum biochemical analysis were unremarkable. A base-apex ECG examination revealed that the heart rate ranged from 40 to 60 beats/min; the rhythm was irregularly irregular with an absence of P waves (Figure 1). These findings were consistent with atrial fibrillation (AF). Echocardiographic variables, including cardiac chamber dimensions, valve morphology, and trans-valvular flow velocities, were within reference limits. On the basis of clinical examination and diagnostic test findings, a diagnosis of lone AF was made.
To convert the AF, the horse was admitted to the hospital for a transvenous electrical cardioversion (TVEC) procedure. Serum electrolyte concentrations were within reference intervals at this time. A baseline serum cardiac troponin I (cTnI) concentration was determined to be normal (0.053 ng/mL; reference interval, < 0.29 ng/mL). A continuous rate infusion of amiodarone hydrochloride (5 mg/kg/h [2.27 mg/lb/h]) was administered IV before the TVEC procedure. While introducers were placed in the right jugular vein for the procedure (after 60 minutes of constant rate infusion with amiodarone), it was noted that the rhythm changed from AF to atrial flutter (AFL), followed by conversion to normal sinus rhythm 10 minutes later. The continuous rate infusion of amiodarone was continued thereafter for 8 hours at a rate of 1 mg/kg/h (0.45 mg/lb/h). The plasma cTnI concentration measured 18 hours after medical conversion of AF to normal sinus rhythm was 0.087 ng/mL, and no abnormalities were observed during a recheck ECG and echocardiographic examinations.
One month after the conversion, a recheck cardiologic examination was performed. The ECG tracing revealed a regular rhythm and a heart rate of 30 to 40 beats/min. The plasma cTnI concentration was 0.027 ng/mL. Ambulatory Holter monitoring was conducted for a 24-hour period and revealed no evidence of cardiac arrhythmia, although the heart rate varied in accordance with the level of exercise performed. Therefore, it was determined that the horse could return to performance. After 7 months with no antiarrhythmic treatment, the horse had remained healthy and in normal sinus rhythm.
ECG Interpretation
At the time of the horse's admission to the hospital, the lead-I base-apex ECG tracing revealed an irregularly irregular heart rhythm, no discernible P waves, fine fibrillation waves in the baseline, and variable atrioventricular (AV) conductions (Figure 1). The QRS-T complexes were of apparently normal duration and morphology. A mean heart rate of 53 beats/min was noted. A ladder diagram was generated and revealed that electrical impulses originated within the atria in an unorganized matter, instead of originating from the sinoatrial node. Most of the impulses propagated to the AV node were blocked because the ventricular response rate of AF is determined by the refractoriness of the AV node. The ladder diagram illustrated irregular rhythmicity, and conduction block was observed in the ECG tracing.
Initial lead-I base-apex ECG tracing and ladder diagram for a horse that was evaluated because of exercise intolerance of 1 week's duration and an irregular heart rhythm. Atrial fibrillation is characterized by irregularly irregular R-R intervals, fibrillation waves in the baseline, and no discernible P waves. In the ladder diagram, the upper zone represents atrial activation (zone A), the middle zone represents atrioventricular (AV) conduction (zone AV), and the lower zone represents ventricular activation (zone V). The vertical lines represent the conduction of the electrical impulses from the AV node to the ventricles, which is responsible for the QRS complexes observed. Notice the multiple ectopic foci within the atria. Functional AV blocks are present and impulses are irregularly propagated to the ventricles. Paper speed = 25 mm/s; 5 mm = 1 mV.
Citation: Journal of the American Veterinary Medical Association 250, 3; 10.2460/javma.250.3.278
The ECG tracing obtained after 60 minutes of constant rate infusion with amiodarone revealed organized and regular flutter (sawtooth-shaped) waves with a flutter rate of 210 beats/min, which was consistent with AFL (Figure 2). There were no discernible P waves, and the rhythm was irregularly irregular. The mean ventricular response rate was 48 beats/min, with QRS complexes of apparently normal morphology and duration. A ladder diagram was generated and revealed that electrical impulses originated within the atria in regular cycle lengths and intervals (representing macro-reentry cycles), which were propagated to the AV node. The blockage of the AV conduction was responsible for inconsistent conduction to the ventricles, which was represented by the irregularly irregular intervals between QRS complexes.
Lead-I base-apex ECG tracing and ladder diagram for the horse in Figure 1 after treatment with a constant rate infusion (5 mg/kg/h [2.27 mg/lb/h]) of amiodarone hydrochloride for 60 minutes. Atrial flutter is characterized by regular flutter waves resulting from macro-reentry circuits within the atria. There are no discernible P waves, and the R-R intervals are irregularly irregular. The electrical impulses within the atria (zone A) originate in regular cycle lengths and intervals, but the impulses in the AV node are blocked, resulting in irregularity of the ventricular depolarization (zone V). Paper speed = 25 mm/s; 5 mm = 1 mV. See Figure 1 for key.
Citation: Journal of the American Veterinary Medical Association 250, 3; 10.2460/javma.250.3.278
Seventy minutes after the start of the constant rate infusion of amiodarone, the AFL converted to normal sinus rhythm (Figure 3). The heart rate was 40 beats/min. There was a distinct P wave preceding every QRS complex, and the QRS complexes were observed at regular intervals. A ladder diagram was generated and revealed that the electrical impulses were originating from the sinoatrial node in regular intervals. There was no AV block of the impulses, resulting in regular ventricular depolarizations.
Lead-I base-apex ECG tracing and ladder diagram for the horse in Figure 1 after treatment with a constant rate infusion of amiodarone for 70 minutes. The sinus rhythm is normal with distinct P waves preceding every QRS complex and regular R-R intervals. In the ladder diagram, the electrical impulses originate within the sinoatrial node and there is no blockage of conduction in the AV node. Paper speed = 25 mm/s; 5 mm = 1 mV. See Figure 1 for key.
Citation: Journal of the American Veterinary Medical Association 250, 3; 10.2460/javma.250.3.278
Discussion
Atrial fibrillation is the most common supraventricular arrhythmia associated with poor performance in horses.1 In AF, the loss of atrial contraction decreases ventricular filling, thereby decreasing stroke volume.2 Horses are predisposed to AF because of their high vagal tone and large atrial mass, which promote the maintenance of multiple reentrant electrical circuits within the atria.3 In addition to structural heart changes, microstructural lesions or channelopathies can also predispose horses to develop AF.4 Conversion to normal sinus rhythm is recommended in equine athletes, especially when the abnormal rhythm persists for > 48 hours.4 Although cardiac output may be adequate at rest in most horses with AF, maximal cardiac output during exercise is diminished in affected horses, leading to the clinical signs of exercise intolerance, exercise-induced pulmonary hemorrhage, or even syncope.1 A short duration of AF as well as the absence of underlying cardiac disease (lone AF) is associated with a higher success rate and better prognosis for conversion to normal sinus rhythm.5,6
The most commonly used methods to manage AF in horses include the administration of quinidine sulfate or TVEC, which have comparable success rates. Quinidine sulfate is a class Ia antiarrhythmic agent with a strong vagolytic effect. Therefore, high blood concentration of this drug can lead to serious cardiac complications, such as rapid supraventricular tachycardia or ventricular arrhythmias.7 In horses, treatment of AF with quinidine sulfate requires close monitoring with continuous ECG, and early changes such as a prolonged QRS complexes are indicative of toxicosis and the need for cessation of the treatment.1 Adverse drug reactions, such as gastrointestinal tract disorders, signs of depression, urticaria, muzzle swelling, or neurologic signs after the administration of quinidine sulfate in horses, have been reported and may require discontinuation of the treatment before cardioversion to normal sinus rhythm is achieved.7,8
Transvenous electrical cardioversion in horses requires placement of catheters in the left pulmonary artery and the right atrium. Anesthetized horses have a defibrillator ECG attached on a base-apex configuration, and the catheters are connected to the defibrillator to deliver shocks that are synchronized with R waves.9 Cardioversion with quinidine sulfate administration requires hours or even days to be achieved, whereas TVEC can result in normal sinus rhythm immediately after sufficient electrical energy is delivered. Complications of the TVEC procedure are related to general anesthesia or electrical shock.1
Amiodarone is a class III antiarrhythmic agent that blocks potassium, sodium, and calcium channels and β-adrenergic receptors.10 Amiodarone is widely used for the treatment of AFL and AF, with minimal adverse cardiac effects in humans.11 In cases of impaired cardiac function, amiodarone has proven to be more efficacious than other pharmacological agents.11,12 Results of a controlled clinical study13 in human patients indicated that amiodarone is safe and effective in the termination of AF, even though patients with a large left atrium and long-lasting arrhythmia needed long-term treatment. In humans, pretreatment with amiodarone has been shown to increase the efficacy of conversion and decrease the recurrence of AF by reversing the partially depolarized diastolic potential of the subsidiary pacemakers.14 Similarly, amiodarone administered to horses with AF as a constant rate infusion before and after a TVEC procedure may promote conversion success rate and decrease the likelihood for recurrence.
In a study15 of horses with chronic AF and without underlying cardiac disease, amiodarone administered at a rate of 5 mg/kg/h successfully converted 4 of 6 horses to normal sinus rhythm with no adverse cardiac effects. Short-term use of amiodarone in horses is unlikely to result in adverse effects,15,16 thereby providing a safe pretreatment option prior to a TVEC procedure. Proarrhythmic effects associated with IV administration of amiodarone in horses have not been reported.15–17 The most commonly reported adverse reactions after amiodarone administration in horses are hind limb weakness and weight shifting that resolve within 6 hours of cessation of the treatment.15 For the horse of the present report, the same amiodarone dosage as that used in a previous study15 was administered with no adverse effects. On the basis of findings for humans with AF treated with amiodarone, it can be speculated that the success rate of conversion to normal sinus rhythm in horses with underlying heart disease or chronic AF may increase with amiodarone treatment.14 Repeated measurements of plasma concentrations of cTnI in the horse of the present report indicated that amiodarone did not cause myocardial damage, which is of importance for return of an equine athlete to its previous performance level.
The case described in the present report illustrated the electrical cardiac events that resulted in normal sinus rhythm during a continuous IV infusion of amiodarone in a horse with AF. In sequence, the ECG tracings reflected changes from AF to AFL and ultimately to normal sinus rhythm as a result of amiodarone administration, a treatment that is not commonly considered for horses with AF. The flutter waves in the ECG tracing obtained after 60 minutes of constant rate infusion (5 mg/kg/h) of amiodarone were indicative of improvement in the organized electrical activity within the atria, which with time progressed to establishment of the normal sinus rhythm. Moreover, the drug treatment resulted in successful cardioversion with no adverse cardiac effects.
References
1. Bonagura JD, Reef VB, Schwarzwald CC. Cardiovascular diseases. In: Reed MS, Bayly WM, Sellon DC, eds. Equine internal medicine. 3rd ed. St Louis: Saunders Elsevier, 2010; 459–463.
2. Blissitt KJ. Diagnosis and treatment of atrial fibrillation. Equine Vet Educ 1999; 11: 11–19.
3. Fenton FH, Cherry EM, Kornreich BG. Termination of equine atrial fibrillation by quinidine: an optical mapping study. J Vet Cardiol 2008; 10: 87–103.
4. Reef VB, Bonagura J, Buhl R, et al. Recommendations for management of equine athletes with cardiovascular abnormalities. J Vet Intern Med 2014; 28: 749–761.
5. Reef VB, Levitan CW, Spencer PA. Factors affecting prognosis and conversion in equine atrial fibrillation. J Vet Intern Med 1988; 2: 1–6.
6. Decloedt A, Schwarzwald CC, De Clercq D, et al. Risk factors for recurrence of atrial fibrillation in horses after cardioversion to sinus rhythm. J Vet Intern Med 2015; 29: 946–953.
7. Jesty SA, Reef VB. Cardiovascular system. In: Orsini JA, Divers TJ, eds. Equine emergencies: treatment and procedures. 3rd ed. St Louis: Saunders Elsevier, 2008; 67–77.
8. McGurrin MKJ, Physick-Sheard PW, Kenney DG, et al. Transvenous electrical cardioversion in equine atrial fibrillation: technique and successful treatment of 3 horses. J Vet Intern Med 2003; 17: 715–718.
9. McGurrin MK, Physick-Sheard PW, Kenney DG. How to perform transvenous electrical cardioversion in horses with atrial fibrillation. J Vet Cardiol 2005; 7: 109–119.
10. Gill J, Heel RC, Fitton A. Amiodarone. Drugs 1992; 43: 69–110.
11. Glover BM, Baranchuk A. Amiodarone for atrial fibrillation: friend or foe? Cardiol J 2015; 22: 603–604.
12. Khan IA, Mehta NJ, Gowda RM. Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation. Int J Cardiol 2003; 89: 239–248.
13. Vardas PE, Kochiadakis GE, Igoumenidis NE, et al. Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study. Chest 2000; 117: 1538–1545.
14. Capucci A, Villani G, Aschieri D, et al. Oral amiodarone increases the efficacy of direct-current cardioversion in restoration of sinus rhythm in patients with chronic atrial fibrillation. Eur Heart J 2000; 21: 66–73.
15. De Clercq D, van Loon G, Baert K, et al. Intravenous amiodarone treatment in horses with chronic atrial fibrillation. Vet J 2006; 172: 129–134.
16. Trachsel D, Tschudi P, Portier CJ, et al. Pharmacokinetics and pharmacodynamic effects of amiodarone in plasma of ponies after single intravenous administration. Toxicol Appl Pharmacol 2004; 195: 113–125.
17. De Clercq D, Loon G, Baert K, et al. Effects of an adapted intravenous amiodarone treatment protocol in horses with atrial fibrillation. Equine Vet J 2007; 39: 344–349.
