A Review of Treatment Options and Prognosis in Equine Atrial Fibrillation

If there is no underlying cardiac disease, atrial fibrillation (AF) in horses generally has a good prognosis for restoration of sinus rhythm and athletic potential. The number of treatment options are increasing, and they include electrical cardioversion. New pharmacologic therapies are also being investigated.

1. Introduction

Atrial fibrillation (AF) remains the most common clinically relevant arrhythmia in the horse [1-3]. Traditionally, treatment has involved the administration of quinidine salts either orally or more recently, intravenously [1-4]. The prognosis has generally been considered to be good as long as the horse does not have underlying cardiac disease and the arrhythmia did not occur for >4 mo. Older and larger horses have been considered to have a reduced prognosis [1-5]. New therapeutic options are now available. These include new medications, such as flecainide [6-8], and non-pharmacologic strategies, such as electrical cardioversion [9,10]. Equine practitioners should be aware of the therapeutic options available for this arrhythmia and of the prognosis both for response to treatment and future athletic performance.

2. AF - the Arrhythmia

AF is a supraventricular arrhythmia; in AF, atrial tissue depolarizes in a disorganized, rapid, and random manner so that coordinated atrial contractions do not occur [11,12]. Diagnosis is suggested by an absolute lack of cardiac rhythm and is confirmed by electrocardiographic findings [11,12]. An irregular ventricular rhythm with normal-looking but irregularly occurring QRS complexes, an absence of P wave, and an undulating baseline with irregular, variable-sized fibrillatory (f) waves are the electrocardiographic criteria for diagnosis of the arrhythmia [11].

The incidence of AF in the horse has been estimated at 0.34 - 2.5% [4,5]. Ventricular rate is often normal in affected horses at rest, a finding attributed to inherently high resting vagal tone. In humans, AF has an incidence of 0.4% in the general population [13,14] and ≤4 - 6% in people >60 yr of age [15]; in contrast, the ventricular rate in the horse is often elevated [11,16].

In most cases of equine AF, there is no evidence of underlying structural heart disease [1,4]. This is again in contrast to people where only 12 - 20% of patients with AF do not have underlying structural cardiac disease [11,16].

A typical presentation for a horse with AF is a sudden onset of poor performance and an irregular cardiac rhythm [1,4,5]. Equine AF is generally a stable arrhythmia, and when present, it persists until therapy is attempted. In occasional cases, the arrhythmia is paroxysmal and starts and stops spontaneously. Paroxysmal AF is difficult both to diagnose and to manage. In humans, a progression of the arrhythmia through multiple recurrences and eventual permanence (non-responsive to any therapeutic intervention) has been well documented [11,16,17]. This progression of the disease has not been documented in the horse.

3. Therapeutic Options

The presence of AF in an otherwise healthy horse does not affect the horse's prognosis for survival. However, performance is limited as long as the arrhythmia persists. At low exercise levels, the horse may perform to expectations, but as exercise intensity increases, the horse exhibits a limited ability to respond to demands. Therefore, performance plateaus well below the animal's usual maximal performance level [1-3]. Restoration of sinus rhythm is necessary to allow return to usual performance. The incidence of recurrence of AF in horses is sufficiently low (10 - 15%), and there is an excellent prognosis for performance when sinus rhythm has been restored. Ongoing medication is not necessary.

4. Pharmacologic Treatment

AF in horses is traditionally treated, either orally or intravenously, with the anti-arrhythmic drug quinidine [1,2,4,5,18]. This agent has a reported efficacy of 83 - 92% [1,2,4,5]. Quinidine (Class IA anti-arrhythmic) has a narrow therapeutic index, variable bioavailability when administered orally, and wide individual variation in half-life in horses [19,20]. Overt signs of toxicity range from mild colic and nasal edema to tachypnea, hypotension, severe tachycardia, collapse, laminitis, diarrhea, and death [21,22]. Depression, inappetence, apprehension, and mild ataxia are considered to be side effects [18,23].

The use of quinidine in the cardioversion of AF in humans has decreased in recent years [11,16]. An increase in mortality in the treated group in a meta-analysis of controlled trials has led to some controversy [11]. The frequency of torsade de pointes in humans treated with quinidine ranges from 1.5% to 8% per patient per year of treatment [24]. Association of this complication with hypokalemia and low heart rate have been reported [11,24].

Flecainide (Class IC anti-arrhythmic) is approved in humans for the treatment only of paroxysmal AF in the presence of a structurally normal heart [11]. Adverse reactions have been reported, and it is recommended that flecainide be avoided in the presence of organic heart disease [16]. Flecainide prolongs mean fibrillation intervals and potentially may convert AF to atrial flutter with increased risk of atrioventricular conduction and rapid ventricular rates [25].

Flecainide has been reported as effective in experimentally induced equine AF of short duration [6,7], but the use of this agent has not been favorable in clinical cases [8]. A report describing the clinical use of flecainide in horses with chronic AF showed limited efficacy with only 1 of 10 horses responding [8]. Severe tachycardia was observed in three horses.

Procainamide and amiodarone pharmacokinetics have been described for horses [26], but no reports of the use of these agents for the treatment of AF in horses are available.

Amiodarone is primarily a Class III anti-arrhythmic that inhibits sodium and calcium channels and possesses anti-adrenergic effects [27]. Amiodarone is considered to be moderately effective for cardioversion in humans [11,28], and it is reported to have a good ventricular rate slowing effect. Adverse effects such as bradycardia, hypotension, and thyroid dysfunction have been noted after oral administration. Torsade de pointes is considered to be rare [29].

Procainamide (Class IA anti-arrhythmic) has been reported as effective in humans for the cardioversion of AF of 24-h duration [11]; however, there is a high rate of spontaneous cardioversion in this time period. Adverse effects are reportedly limited to hypotension. This agent has not been well tested in persistent AF.

Propafenone (Class IC anti-arrhythmic) compared with placebo has proven effective in the conversion of recent-onset AF in humans, but it seems to have reduced efficacy in arrhythmia of longer durations and in the presence of structural heart disease.

5. Electrical Cardioversion

Electrical cardioversion of AF involves the application of a direct current shock synchronized with the R wave to ensure that the shock is not applied near the T wave, the susceptible period for ventricular fibrillation. Animal and human studies show an incidence of ventricular fibrillation of ≤2% [11,30].

Biphasic shocks, which deliver a positive followed by a negative waveform, have been shown to be more effective than monophasic shocks, and lower energy levels are required to achieve cardioversion [11,30].

Attempted electrical cardioversion with external pads and paddles has recently been described in two horses, one of which responded to therapy [31]. The procedure involved positioning the horse in dorsal recumbency under general anesthesia with suspension of the limbs to allow safe and unimpeded access to both sides of the thorax. Successful treatment was assisted by simultaneous administration of anti-arrhythmic medications. Electrical cardioversion was previously considered to be ineffective in the horse.

Transvenous electrical cardioversion has been attempted in horses at the Ontario Veterinary College [10,31,32]. Cardioversion catheters were placed through the right jugular vein and positioned with the electrodes in the pulmonary artery and in the right atrium. In the initial phase of the study, cardioversion was achieved in a horse with AF duration for 3.5 yr. Subsequently, a clinical trial was pursued. Modifications to catheter placement techniques and catheter design were made during the application of this procedure to eight horses. Cardioversion was achieved in seven of these animals. Other horses were then treated with the technique developed in this trial. Currently, 42 client-owned horses have been treated with AF duration ranging from 1 wk-1 yr. Underlying cardiac disease aside from mild valvular regurgitation was absent in most cases. All cardiac dimensions were normal. Cardioversion has been achieved in 41 horses with 38 back in full training or competition. Additionally, cardioversion has been achieved in one horse with AF duration of 7 yr. Recurrence of AF occurred in five horses, four of which were cardioverted again. AF has not recurred to date in the three horses with AF duration >1 yr. Long-term performance outcomes have not been reported for cases cardioverted pharmacologically, but it is unlikely that they would differ from the outcomes after electrical cardioversion. Arrhythmias after electrical cardioversion are reported in humans [11,30]. Mild, generally benign arrhythmias such as premature beats, bradycardia, and even short duration sinus arrest often subside without intervention. Atrial stunning, where recovery of left atrial mechanical function is delayed by ≤24 h [33], has been reported after both electrical and pharmacologic cardioversion in humans. Acute pulmonary edema has been reported after electrical cardioversion of AF in humans [34]. This complication is considered to be rare. Pre-existing hypertension and valvular heart disease are present in most cases. Severe left atrioventricular valve dysfunction increases left atrial pressure, which may elevate pulmonary venous pressure and increase the risk for pulmonary edema. To date, only transient atrial premature contractions have been observed after transvenous electrical cardioversion in horses.

6. Prognosis

The prognosis for restoration of sinus rhythm in horses with AF is excellent providing that there is no underlying cardiac disease, such as cardiac enlargement or severe valvular regurgitation. Quinidine efficacy is between 75% and 85%. With transvenous electrical therapy, the efficacy to date is 98%. With quinidine therapy, reduced efficacy in older, larger horses or in those animals with AF duration >4 mo has been reported. Further investigation into the use of flecainide is necessary before the efficacy and safety of this medication is known. With response to electrical therapy in horses with AF durations of 3.5 and 7 yr, the generally accepted relationship between duration of arrhythmia and prognosis for cardioversion should be reconsidered. The prognosis for return to previous performance after cardioversion in uncomplicated cases is excellent, regardless of treatment, although long-term performance needs to be investigated. Athletic potential of successfully treated horses with prolonged arrhythmia durations (1 yr plus) requires further investigation. The availability of additional therapeutic options for horses not responsive to, intolerant of, or unlikely to be responsive to quinidine improves the prognosis for horses with AF.

The authors received funding for early investigations into transvenous electrical cardioversion from the Grayson Jockey Club Research Foundation and from the Ontario Ministry of Agriculture and Food. Rhythm Technologies is a continued partner in these investigations.