By Rebecca Quinn, DVM, DACVIM (Cardiology)
Atropine is an anticholinergic agent that works by directly preventing acetylcholine binding to muscarinic receptors. By blocking acetylcholine at its receptor site, parasympathetic signals to the central nervous system, autonomic ganglia, and smooth muscles are blocked. Muscarinic receptors are present in a variety of body tissues and organs, including the heart. The cardiac consequences of atropine administration in a normal patient include increased heart rate, increased cardiac output, and potentially an increase in blood pressure. Atropine is often used in bradycardias to help characterize arrhythmias and determine if interventional procedures such pacemaker placement are necessary.
Common Bradyarrhythmias in Canine and Feline Patients
The most common pathological bradyarrhythmia noted in both dogs and cats is 3rd degree atrioventricular block (3AVB), which is sometimes referred to as complete heart block or complete atrioventricular dissociation. In 3AVB the conduction signal leading from the atria to the ventricles is blocked, and the atria and ventricles beat independently via their own pacemakers. In both species, the atrial rate tends to remain normal due to preserved sinus node function; the atrial rate in dogs with 3AVB ranges from 80 – 140 bpm while the atrial rate in cats ranges from 150 – 200 bpm. During 3AVB, the Purkinje fibers most often control the ventricular heart rate and fire completely independently of the sinus node. This means that in dogs the ventricular heart rate is often as low as 40 bpm, while in cats the ventricular heart rate remains faster and often higher than 100 bpm. It is for this reason that dogs are often much more symptomatic for 3AVB compared to their cat counterparts.
Figure 1. Lead II ECG recording (50 mm/s, 10 mm/mV) of a dog with 3rd degree atrioventricular block. The sinus node (P waves) rate is approximately 160 bpm, and the P waves are not associated with the QRS complexes. The ventricle rate is approximately 40 bpm. This patient suffered from syncopal events as a result of profound bradycardia.
Figure 2. Lead II ECG recording (50 mm/s, 10 mm/mV) of a cat with 3rd degree atrioventricular block. The sinus node (P waves) rate is approximately 214 bpm, and the P waves are not associated with the QRS complexes. The ventricle rate is approximately 160 bpm. This patient was asymptomatic for 3rd degree atrioventricular block, and the arrhythmia was identified incidentally as part of pre-surgical screening.
Second degree atrioventricular block (2AVB) is also common, although noted more in dogs than in cats. In 2AVB, the sinus node fails to conduct to the ventricles sometimes but not all the time, meaning that some P waves are associated with QRS complexes while others are not. Second degree AVB may be Mobitz Type I or II. In 2AVB Mobitz Type I, the PR interval slowly increases in duration until the sinus node fails to conduct to the ventricle. In 2AVB Mobitz Type II, the PR interval is constant and some P waves fail to conduct. Furthermore, 2AVB Mobitz Type II can be characterized by the number of P waves that ultimately result in a conducted P-QRS. For example, if every other P wave conducts, the pattern is referred to as 2:1 (two P waves for every conducted QRS). If 3 P waves occur before one conducts, this is referred to as 3:1 (3 P waves for every conducted QRS). As the ratio becomes higher, the likelihood of clinical signs (weakness, collapse) increases.
Figure 3. Lead II ECG recording (25 mm/s, 10 mm/mV) of a dog with 2nd degree atrioventricular block. Note that the PR interval slowly increases (lengthens in duration) until a P wave is conducted without an associated QRS. This is 2AVB Mobitz Type I; every second P wave results in a conducted P-QRS, therefore this arrhythmia can be further characterized as 2:1 conduction. This patient was asymptomatic for bradycardia.
Figure 4. Lead II ECG recording (50 mm/s, 20 mm/mV) of a cat with 2nd degree atrioventricular block. When present the PR interval is constant, indicating this is 2AVB Mobitz Type II; every second P wave results in a conducted P-QRS, therefore this arrhythmia can be further characterized as 2:1 conduction. This patient was asymptomatic for bradycardia.
Sick sinus syndrome (SSS) can be characterized by periodic tachycardia and abrupt bradyarrhythmia. It is for this reason that SSS is often referred to as tachy-brady syndrome. The bradyarrhythmia in SSS is often a long pause (several seconds long) with ventricular escape complexes. Sick sinus syndrome is more common in dogs, particularly West Highland White Terriers and Miniature Schnauzers, and not reported frequently in cats. Patients with SSS are often diagnosed based on auscultation, but are more commonly evaluated for collapse events; collapse events in SSS may be triggered by either tachycardia or bradycardia.
Figure 5. Lead II ECG recording (50 mm/s, 10 mm/mV) of a dog with sick sinus syndrome. The patient’s heart rate is initially sinus with a rate of approximately 130 bpm. The sinus node suddenly fails, resulting in a long pause interrupted by ventricular escape beats. This patient presented for multiple collapse episodes, and the collapses were confirmed to occur during periods of profound bradycardia (pauses lasting 5 seconds).
Atrial standstill is the complete lack of sinus node function, which results in absent P waves. This can be due to systemic disease (hyperkalemia) but can also be secondary to severe heart disease. English Springer Spaniels are over represented, and often have very severe atrial myopathy.
Figure 6. Lead II ECG recording (50 mm/s, 10 mm/mV) of a cat with atrial standstill. Note the lack of P waves; this patient’s heart rate is completely generated by the ventricles and a rate of 85 bpm. This patient had severe acquired cardiac disease but no complaints of weakness or collapse.
Atropine Response Test Interpretation
Atropine is often given to dogs and cats with a variety of bradyarrhythmias to challenge the cardiac conduction system. This helps determine if the bradyarrhythmia, particularly those described above, are secondary to systemic disease (high parasympathetic or vagal tone) or due to primary cardiac conduction disturbances or cardiac disease. It is important to note that all patients with bradyarrhythmias should have thorough physical exams evaluating for non-cardiac illness as well as baseline labwork prior to an atropine response test (ART). This includes electrolytes, complete blood count, and general chemistry panel. In some patients, additional labwork such as infectious disease testing or endocrine testing may also be warranted. Other than ECG, these patients may benefit from echocardiogram or thoracic radiographs.
Assuming there is no obvious concurrent illness, such as hypoadrenocorticism resulting in hyperkalemia and atrial standstill, ARTs can be performed by giving either subcutaneous or intravenous injections. Given the potential side effects of atropine, including worsening tachyarrhythmia, hyperpnea, and respiratory depression, ARTs at Angell are completed in patients only after intravenous catheter placement and using the intravenous injection method. Particular caution is used in patients with SSS, as atropine may worsen periods of tachycardia and result in patient decompensation. During ARTs, patients are placed in right lateral recumbency with a 6-lead ECG system attached. Atropine is given at a dose of 0.04 mg IV once, and the ECG is monitored continuously for 15 minutes. If no change in the bradyarrhythmia is noted after 15 minutes, atropine is repeated at 0.04 mg/kg IV and the patient monitored for 15 more minutes.
A successful or “positive” ART results in abolishing the bradyarrhythmia. In other words, the administration of atropine overcomes the bradyarrhythmia, and the patient transitions from bradycardia to a sinus rhythm or tachycardia during the 15 – 30 minute ART. More specifically, a positive ART includes inducing normal P-QRS conduction and also increases the sinus rate by double or >150 bpm.
Figure 7. Lead II ECG recording (50 mm/s, 10 mm/mV) of a dog with 2nd degree atrioventricular block Mobitz Type I. The patient presented for evaluation of lethargy and vomiting, and an arrhythmia was noted by the primary clinician. Panel A is prior to atropine therapy, while Panel B is 2 minutes post atropine injection. In Panel B, each P wave conducts to a QRS, the overall sinus rate increases, and the ventricular rate increases to 214 bpm. This patient’s ART was considered positive, and the arrhythmia was due to increased vagal tone. Further testing identified an abdominal mass, and after surgical resection and recovery, the patient’s arrhythmia did not recur and sinus rhythm was maintained without further medical intervention.
Interestingly, some patients may have partially positive ARTs. An example of this would include a patient whose overall heart rate improves, but heart block still persists or the heart rate does not double or increase appropriately. This is not very common, but does occur. These patients may have early cardiac conduction disturbances, or vagal tone that is very difficult to overcome. Most often these patients are not symptomatic for their arrhythmias, and are monitored periodically via ECG for worsening bradycardia.
Figure 8. Lead II ECG recording (25 mm/s, 10 mm/mV) of a dog with 2nd degree atrioventricular block Mobitz Type II with 2:1 conduction. The patient presented for evaluation of a grade II/VI left apical systolic murmur and bradyarrhythmia. The patient was diagnosed with ACVIM Consensus Class B2 mitral valve endocardiosis. Panel A is prior to atropine therapy, while Panel B is 4 minutes post atropine injection. In Panel B, each P wave conducts to a QRS, the overall sinus rate increases, and the ventricular rate increases from 65 to 125 bpm. This patient’s ART was considered partially positive, as the arrhythmia improved but the heart rate did not double or exceed 150 bpm. This patient was monitored every 6 months; over time the patient’s heart rate decreased, but she remained partially responsive to atropine. Oral terbutaline therapy was used to maintain an adequate heart rate at home.
A negative ART is the failure of atropine to alter the heart rate or abolish a bradyarrhythmia. In these cases, bradyarrhythmia persists despite two intravenous doses of atropine given over 30 minutes. Assuming all other diagnostics are normal, this is an indication that the arrhythmia is due to primary cardiac disease. While an echocardiogram could be considered in any patient with a bradyarrhythmia, in cases of negative ARTs an echocardiogram should absolutely be performed. A negative ART indicates that at-home oral therapies such as anticholinergics or beta-agonists will not be helpful. If the patient is symptomatic and experiencing lethargy, weakness, or collapse, pacemaker therapy is often indicated. Likewise, pacemaker therapy is also indicated if chronic bradycardia results in bradycardia induced cardiac dilation or low output congestive heart failure. As noted above, cats often tolerated primary cardiac arrhythmias such as 3AVB without any clinical issues; pacemaker placement in cats is possible but is less frequently indicated compared to dogs.
Figure 9 Lead II ECG recording (50 mm/s, 10 mm/mV) of a dog with 3rd degree atrioventricular block. The patient presented increased respiratory rate and effort as well as episodes of collapse. Panel A demonstrates 3AVB with failed response to atropine. The patient was diagnosed 3AVB leading to cardiac dilation and congestive heart failure. The congestive heart failure was initially controlled with supportive care (oxygen, diuretics, positive inotropes), and twenty-four hours later a transvenous endomyocardial pacemaker was placed. Panel B demonstrates the heart rate and rhythm after pacemaker implantation; note the small negative (downward) pacing spikes immediately prior to each QRS complex. The patient’s cardiac structures improved with pacemaker therapy, and diuretics and positive inotropes were discontinued over time. The patient remained stable and died of non-cardiac causes 3 years later.
Atropine response tests are commonly used to evaluate patients with asymptomatic and symptomatic bradyarrhythmias. By administering an anticholinergic therapy, one can often determine if an arrhythmia is secondary to systemic disease or due to primary cardiac disease. Patients that have a positive response to atropine are more likely to have non-cardiac illness and arrhythmias due to high parasympathetic tone. These patients, along with those who have partial responses to atropine, may benefit from oral anticholinergics or beta-agonists. Patients who remain bradycardic despite atropine administration are more likely to have primary cardiac disease and may require pacemaker therapy.
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