12 Oct 2015
David Mills
Job Title
Figure 2: ECG from a dog with AF. There is an absence of waves and, where visible, the baseline undulates coarsely. The R-R intervals are irregularly irregular. The QRS complexes are wide and tall, suggestive of left ventricle enlargement, which fitted with a dilated cardiomyopathy phenotype in this dog. Ventricular rate was, on average, 200bpm. 25mm/sec, lead II.
Atrial fibrillation (AF) occurs almost exclusively in left atrial enlargement secondary to acquired heart disease. It normally occurs late in the disease process.
Its prevalence in dilated cardiomyopathy (DCM) varies from 30% to 71% in both clinical and subclinical forms1-3.
Prevalence of AF in the absence of structural heart disease/left atrial enlargement, so-called “lone AF”, is only 0.05%6.
In cases of CHF due to MMVD or DCM, the presence or development of AF is associated with a worsening of the CHF, increased morbidity and decreased survival times5-8.
The ventricular tachycardia produced by AF can lead to significant increases in myocardial oxygen demand, leading to ischaemic damage and myocardial cell exhaustion. It also prevents effective ventricular filling during diastole.
On auscultation, AF is classically characterised by a chaotic tachycardia. An ECG confirms diagnosis (Figures 1 and 2), with the following features:
No studies document greater survival with either rhythm or rate control in dogs. Human studies have shown rate control to be as effective as rhythm in morbidity and mortality terms, with a tendency for lower mortality11,12.
Pharmacological rhythm control in animals (for example, with amiodarone) lacks sufficient data and safety profiling14.
Rate control remains the treatment of choice from an evidence-based perspective in dogs. A recommendation is to aim for heart rates (HR) less than 140bpm to 160bpm. However, this is not supported by evidence.
HR remains a surrogate outcome, with no published studies detailing target ranges or, importantly, how these relate to quality of life or survival times. Much is extrapolated from human medicine, which may lack applicability given the lower HR.
Work has also caused a re-evaluation of the size/HR dogma for dogs, which has further complicated matters15. Daily at-home HR measurement can provide more useful monitoring data than HRs taken from an excited dog in clinic, but can also be subject to unreliability, with poor agreement even between veterinary surgeons for HR estimates in AF16.
In-house spot ECGs are considered poor monitors of HR, given the surroundings, and typically produce results 20bpm to 30bpm higher than true at-home (Holter) rates9. Holter monitoring can be considered, but use may be limited by financial considerations.
Digoxin (3µg/kg to 7µg/kg every 12 hours PO, reduce doses by 10% for liquid formulations) represents the traditional mainstay of AF therapy, though there is no evidence for it improving survival times or quality of life in dogs.
Digoxin is a parasympathomimetic (and, less so, an inhibitor of the sympathetic nervous system), which decreases heart rate mainly through inhibition of AV node conduction and, to a lesser extent, slowing sinoatrial node firing17.
It may also provide mild inotropic effects via its Na+/K+-ATPase inhibition, which leads to a rise in intracellular calcium and a mild increase in force of contraction. It “resets” baroreceptor activation seen in CHF, which helps lower renin-angiotensin-aldosterone system (RAAS) activation.
Digoxin alone may not provide adequate rate control over 24 hours, especially during periods of increased sympathetic tone such as excitement or exercise. In one study HR remained above 140bpm for 88% of a 24-hour recording period18.
Side effects such as vomiting, diarrhoea and lethargy are common. Digoxin is also pro-arrhythmic given its disruption of calcium homeostasis and can cause a range of atrial and ventricular arrhythmias.
In humans, it has been shown clinical efficacy can be maintained with serum levels below laboratory reference ranges with fewer side effects19.
It is recommended to check trough serum levels (eight hours to 12 hours post-pill) five to seven days after starting therapy. The ideal range is 1ng/ml to 2ng/ml to minimise side effects and maximise therapeutic benefits.
Hypokalaemia can potentiate toxic effects, so it is wise to check potassium levels especially when furosemide is being used for CHF therapy. Dose intervals may need to be increased in geriatric animals.
Diltiazem is a relatively cardiotropic calcium channel blocker that slows conduction at the AV node independent of autonomic stimulation. It also causes vascular smooth muscle (especially arterial/arteriolar) relaxation, reducing afterload.
It shows similar efficacy to digoxin for rate control as a monotherapy18.
One study showed satisfactory control of clinical signs in the absence of side effects (hypotension and AV block), with significant reduction in HR, though as with digoxin monotherapy, HRs remained above 140bpm for 88% of the time18. It has traditionally been viewed with caution in veterinary cardiology due to possible negative inotropic effects, though it is commonly used in combination with digoxin in human patients to achieve superior control to either drug alone20,21.
Diltiazem generally shows fewer side effects than digoxin – the main one being lethargy. It can cause AV block and acute decompensation so it is recommended to start at lower dose rates and increase if insufficient response is seen.
Diltiazem is available as a short-acting cat-licensed product. Various human sustained release forms are available, which can be given less frequently, though detailed pharmacokinetic data is unavailable for dogs.
The dose rate for the short-acting form is 0.5mg/kg to 2mg/kg q8hr and the sustained release form has been widely used at 3mg/kg q12hr.
In a trial by Gelzer et al – one of the very few trials of AF therapy in veterinary medicine – digoxin and diltiazem were shown to provide greater control of HR when used together as opposed to monotherapy18. In this study, a median HR in 18 dogs of 194bpm was reduced by digoxin alone to 164bpm, diltiazem alone to 158bpm and by combination therapy to 126bpm (p<0.008).
Digoxin was used at a dose rate of 5µg/kg q12hr, diltiazem sustained release at 3mg/kg q12hr and the dual digoxin-diltiazem therapy was at the same doses.
No dogs showed adverse effects from combination therapy. From an evidence-based perspective, this combination is the best-supported primary therapy for AF in dogs.
Beta-blockers are used in AF primarily due to their effects of slowing AV node conduction and, to lesser extent, suppressing atrial ectopy.
They have shown effective rate control in a retrospective study in dogs, used either alone or in combination with digoxin7. Beta-blockers are an effective therapy in humans alongside digoxin21,22. There are cardiac side effects, however, including reduced contractility, ventricular relaxation and some pro-arrhythmic properties.
Cardiac output has been shown significantly reduced during times of cardiac stress in dogs with AF treated using the beta-blocker propranolol23. They should be used cautiously in CHF and the recommendation is to start at lower doses and increase slowly (every five to seven days). Their use in DCM at low doses is anecdotally thought to improve survival, meaning they may carry additional beneficial effects in dogs with DCM and AF.
Various beta-blockers are available and a full review is beyond the scope of this article; however, effects on AV node conduction seem to be fairly consistent though care should be taken with those agents with multiclass action (for example, sotalol).
Amiodarone is a class III anti-arrhythmic with potent class II and some class IV effects. In a retrospective study involving eight dogs with AF, amiodarone successfully and permanently converted some dogs to sinus rhythm; in others it successfully reduced the HR25.
Oral therapy appears to be very well tolerated, but disadvantages include a very long half-life and slow onset of action; previous concerns about its safety profile seem to be unfounded25.
With its class II (beta-blocking) actions, care must be taken in cases of CHF and bradycardia can occur due to its wide number of class effects. Further studies are needed to illustrate its full efficacy, but amiodarone is potentially a very effective treatment for AF.
Current dose recommendations are a loading dose of 10mg/kg to 15mg/kg q12 hrs for seven days, then 5mg/kg to 7.5mg/kg q12 hrs for 14 days, then 5mg/kg to 7.5mg/kg every 24 hours continuously.
Radioablation of the AV node with pacemaker implantation is a very effective therapy for permanent rate control where pharmacological means fail.
It has been practised widely in humans with success equal to, or greater than, pharmacological therapy26.
It has been used in dogs with published success and is available in several referral centres27. It requires general anaesthesia so may only be suitable for those dogs with early or well-controlled CHF.
