Introduction

A 1-year-old 20.2-kg neutered male mixed-breed dog was presented to the emergency service at the BluePearl Pet Hospital in New Braunfels, Texas, because of acute collapse and lethargy. On presentation, the dog was quiet, dull, and responsive. Cardiac auscultation revealed severe tachycardia (350 beats/min) with a regular rhythm and no murmur. Bronchovesicular sounds were considered normal. Femoral pulses were weak, and frequent pulse deficits were detected. A lead II ECG tracing was obtained (Figure 1).

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Initial lead II ECG tracing obtained from a 1-year-old mixed-breed dog following an episode of acute collapse and lethargy. Notice the wide, bizarre QRS complexes and markedly increased heart rate (350 beats/min). P waves are absent. Paper speed = 25 mm/s; 1 cm = 1 mV.

Citation: Journal of the American Veterinary Medical Association 260, 15; 10.2460/javma.21.01.0062

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ECG Interpretation

The initial lead II ECG tracing (Figure 1) revealed wide QRS complex tachycardia with a heart rate of 350 beats/min. The ventricular coupling interval was regular (170 milliseconds), and the QRS complex duration was markedly prolonged (160 milliseconds; reference range, ≤ 70 milliseconds). Differential diagnoses for the wide QRS complex tachycardia included ventricular tachycardia (VT), supraventricular tachycardia (SVT) with aberrant conduction, and SVT with antegrade conduction over an accessory pathway.¹ Given the rapid heart rate and clinical evidence of hemodynamic compromise, a lidocaine bolus (2 mg/kg, IV) was administered. The heart rate decreased to 260 beats/min, but the wide QRS complex tachycardia persisted, which prompted administration of 2 additional lidocaine boluses (2 mg/kg, IV) approximately 10 minutes apart. Conversion to a normal sinus rhythm occurred, and a constant rate infusion of lidocaine (75 μg/kg/min, IV) was initiated.

Focused cardiac ultrasonography revealed thickened left ventricular walls with a reduced left ventricular chamber size, subjectively decreased right atrial and ventricular chamber sizes, and no pericardial effusion. A focused abdominal ultrasonographic examination revealed gallbladder wall edema with scant peritoneal effusion adjacent to the liver. Thoracic radiography showed no cardiac or pulmonary abnormalities. A CBC and serum biochemical panel revealed a markedly high alanine aminotransferase activity (1,568 U/L; reference range, 10 to 125 U/L), mildly increased BUN concentration (43 mg/dL; reference range, 7 to 27 mg/dL), hyponatremia (136 mmol/L; reference range, 144 to 160 mmol/L), hypochloremia (103 mmol/L; reference range, 109 to 122 mmol/L), hypoalbuminemia (2.2 g/dL; reference range, 2.3 to 4.0 g/dL), high alkaline phosphatase activity (223 U/L; reference range, 23 to 212 U/L), and leukocytosis (21.70 X 10³ WBCs/μL; reference range, 5.05 to 16.76 X 10³ WBCs/μL) characterized by neutrophilia (15.99 X 10³ neutrophils/μL; reference range, 2.95 to 11.64 X 10³ neutrophils/μL) and monocytosis (2.66 X 10³ monocytes/μL; reference range, 0.16 to 1.12 X 10³ monocytes/μL). Prothrombin time (21 seconds; reference range, 11.0 to 17.0 seconds) and partial thromboplastin time (107 seconds; reference range, 72.0 to 102.0 seconds) were both slightly prolonged. Results of other clinicopathologic tests were within reference limits.

At this point, a clinical diagnosis of anaphylaxis was made, and the dog was provided supportive care consisting of crystalloid IV fluid resuscitation, famotidine (1 mg/kg, IV, q 12 h), diphenhydramine (2 mg/kg, IM, q 8 h), and a single dose of dexamethasone sodium phosphate (0.2 mg/kg, IV).

A lead II ECG tracing was obtained 2 hours after the initiation of the lidocaine constant rate infusion (Figure 2), and conversion to a normal sinus rhythm was evident. The heart rate was 149 beats/min, and the PR intervals were consistently prolonged (180 milliseconds; reference range, 60 to 130 milliseconds), suggestive of first-degree atrioventricular (AV) block. An additional lead II ECG tracing was obtained 7 hours after initiation of the lidocaine constant rate infusion (Figure 3). The underlying rhythm was an accelerated idioventricular rhythm with a discharge rate of 136 beats/min. There was AV dissociation with variable PR intervals. A capture beat was noted, which reflected normal conduction of an impulse from the sinus node to the ventricles in the midst of AV dissociation. The ventricular ectopic complexes had a right bundle branch block morphology that was different from the morphology of complexes seen on the ECG recording obtained at the time of admission, indicative of pleomorphism² (ie, variations in QRS complex morphology of monomorphic VTs or ventricular rhythms at different times in the same patient).

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Additional lead II ECG tracing obtained 2 hours after initiation of a lidocaine constant rate infusion. The heart rate has decreased to 149 beats/min, and the P waves and QRS complexes are of normal morphology. The QRS complex duration is 40 milliseconds (reference range, ≤ 70 milliseconds), but the PR interval is prolonged (180 milliseconds; reference range, 60 to 130 milliseconds), consistent with first-degree atrioventricular block. Paper speed = 25 mm/s; 1 cm = 1 mV.

Citation: Journal of the American Veterinary Medical Association 260, 15; 10.2460/javma.21.01.0062

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Additional lead II ECG tracing obtained 7 hours after initiation of the lidocaine constant rate infusion. Notice the accelerated idioventricular rhythm with a discharge rate of 136 beats/min. There is atrioventricular dissociation with variable PR intervals. A capture beat is identified at the beginning of the tracing (asterisk). The ventricular ectopic complexes have a right bundle branch block morphology that is different from the morphology of complexes seen on the initial ECG tracing. This phenomenon is called pleomorphism. Paper speed = 25 mm/s; 1 cm = 1 mV.

Citation: Journal of the American Veterinary Medical Association 260, 15; 10.2460/javma.21.01.0062

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The dosage of lidocaine was slowly tapered, and treatment with sotalol (1 mg/kg, PO, q 12 h) was begun for continued management of the arrhythmia. The dog improved clinically and was discharged the next day with prescriptions for sotalol (1 mg/kg, PO, q 12 h), famotidine (1 mg/kg, PO, q 12 h), diphenhydramine (2.5 mg/kg, PO, q 8 h), and prednisone (0.5 mg/kg, PO, q 12 h initially with a gradual reduction in dosage). Serum was submitted for measurement of cardiac troponin I concentration, which was markedly increased (27.8 ng/mL; reference range, ≤ 0.06 mg/mL). Serum digoxin concentration was also measured in light of the owner’s concerns about possible oleander toxicosis and was low (0.2 ng/mL; reference range, 0.8 to 2.0 ng/mL). Serum anti–Trypanosoma cruzi antibody titer was 320:1, which was consistent with a diagnosis of American trypanosomiasis (Chagas disease).

The dog was rechecked by its regular veterinarian 2 days after initial discharge, at which time results of a physical examination were reportedly unremarkable and no arrhythmia was auscultated. The owner reported during a telephone conversation 3 weeks after discharge that the dog was clinically normal with no clinical signs of cardiac disease. The owner declined additional diagnostic testing and treatment at that time.

Discussion

The dog of the present report was examined because of wide QRS complex tachycardia. Differential diagnoses for wide QRS complex tachycardia include VT, SVT with anatomical or functional aberrant conduction, and SVT with antegrade conduction over an accessory pathway.¹ Differentiation relies on clinical context and ECG features during periods of tachycardia and sinus rhythm, although electrophysiologic studies are sometimes necessary for a definitive diagnosis.² Ventricular tachyarrhythmias commonly occur in dogs with organic heart diseases such as degenerative valve disease, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and trypanosomiasis.^3,4 Noncardiac causes include systemic disease, electrolyte imbalances, and drug administration.³ Several types of SVT can have wide QRS complex morphology, but this is considered far less common than with VT.⁵ The characteristic ECG features indicative of VT rather than SVT include capture beats, fusion complexes, and AV dissocation.¹ These features, however, are not always present, and their absence does not rule out VT.¹ The dog of this report presented with a sustained tachyarrhythmia, which made it difficult to determine the presence of these features on the initial ECG tracing. The QRS morphology during sinus rhythm in the dog of this report was normal, which virtually excluded the possibility of SVT with preexisting bundle branch block. There was an accelerated idioventricular rhythm with a change in QRS morphology (pleomorphism), which suggested that the initial tachycardia was also more likely ventricular in origin.² The rapid conversion to sinus rhythm following lidocaine administration also indicated that VT was more likely because lidocaine is most effective for VT and has little effect on SVT. However, it is important to note that successful conversion to sinus rhythm by lidocaine is sometimes possible in cases in which an accessory pathway is involved.⁶ Lidocaine can also be effective for vagally mediated SVTs.⁷

The dog in this report tested positive for trypanosomiasis and had clear evidence of anaphylaxis. The diagnosis of anaphylaxis in this case was established on the basis of the acute onset of hemodynamic instability and the presence of biomarkers associated with anaphylaxis in dogs (eg, high alanine transaminase activity and gallbladder wall abnormalities).⁸ Each condition can cause malignant ventricular arrhythmias through its own distinctive mechanisms, which makes it difficult to definitively explain the cause-and-effect relationship. Our conclusion is that because the dog had no clinical signs of cardiac disease prior to the anaphylactic event and no evidence of the cardiac structural remodeling expected with trypanosomiasis (eg, dilated cardiomyopathy and cardiac chamber enlargement), anaphylaxis probably initiated arrhythmia by its arrhythmogenic and deleterious cardiovascular effects, and the arrhythmia was escalated into sustained VT due to subclinical myocarditis secondary to trypanosomiasis which ultimately provided a substrate and served as a perpetuating factor.

Trypanosomiasis is a zoonotic infection caused by a protozoan hemoflagellate, T cruzi, and transmitted via a vector known as the “kissing bug.” The parasite causes chronic myocarditis, dilated cardiomyopathy, malignant arrhythmia, and subsequent cardiac failure. It is most common in south and central America. Three distinct stages of trypanosomiasis have been described: acute, latent, and chronic. Dogs in the acute phase develop nonspecific signs and acute myocarditis that is usually not clinically evident. Sudden death related to cardiac failure is rare in this phase. The latent phase is typified by absent or only mild clinical signs, and some dogs remain in this phase for life. The chronic phase is characterized by development of chronic myocarditis, dilated cardiomyopathy, malignant arrhythmias of various types, and right-sided or biventricular heart failure. Treatment is mostly supportive therapy for heart failure and arrhythmias. To date, it is unclear whether parasite-specific therapy improves survival time or rate.⁴

Anaphylaxis is an acute potentially fatal systemic hypersensitivity reaction secondary to exposure to an allergy-causing substance. Common causes of anaphylaxis in dogs include insect envenomation, vaccination, and exposure to certain drugs or food.⁹ Interestingly, kissing bug salivary antigens are known to cause anaphylaxis in humans.¹⁰ Repetitive kissing bug bites could explain both anaphylaxis and a diagnosis of trypanosomiasis in the present case. A wide range of cardiac arrhythmias are known to occur secondary to anaphylaxis in humans, including atrial fibrillation, AV block, bundle branch block, and malignant ventricular arrhythmias.¹¹ On the other hand, there are very few reports of malignant arrhythmias secondary to anaphylaxis in dogs. Junctional capture bigeminy was reported in a dog with anaphylaxis due to a bee sting.¹² We attribute the interspecies difference in the prevalence of arrhythmias to the fact that the dominant shock organs are the heart and lungs in humans, compared with the liver and gastrointestinal tract in dogs.⁹ The mechanisms by which anaphylaxis causes arrhythmias are complex and involve various chemical mediators released by cardiac mast cells.¹³ Among these, histamine plays a major role in the development of cardiac arrhythmias and coronary hemodynamic compromise.^11,13,14 Histamine release leads to enhanced automaticity and development of ectopic pacemakers with a resultant predisposition to reentry and after-depolarization.^11,14 Renin and chymase also contribute to the development of arrhythmias by activating the cardiac renin-angiotensin system and enhancing the sympathetic nervous system.¹³

Pleomorphism reflects changes in the direction of ventricular myocardium activation associated with single or multiple reentrant circuits and is typically seen following myocardial infarction.¹⁵ Trypanosomiasis has been associated with myocardial infarction,¹⁶ and the markedly increased troponin concentration in our dog was supportive of acute myocardial injury.¹⁷ Anaphylaxis is also known to cause myocardial infarction, a phenomenon called Kounis syndrome. Kounis syndrome is an acute coronary syndrome associated with anaphylaxis and is characterized by coronary artery spasm with angina, myocardial infarction, and stent thrombosis.¹⁸ One study¹⁹ in human medicine demonstrated that the degree of increase in troponin concentration correlates with the severity of the allergy reaction.

The cause of first-degree AV block in the present case was unclear. Common causes of first-degree AV block in dogs are heightened vagal tone, toxin ingestion, drug ingestion, electrolyte disturbances, and fibrosis of the AV node.²⁰ Trypanosomiasis can cause various types of AV block secondary to myocarditis.^4,21 Alternatively, lidocaine could have triggered a temporary AV block. One experimental study in 8 dogs showed clear evidence of increased conduction time between the sinoatrial node and upper His bundle after lidocaine administration,²² which may manifest as first-degree AV block. Furthermore, several cases exist in the human literature that indicate a possible correlation between lidocaine administration and AV conduction disturbances.^23,24 Histamine can also cause AV block by its dromotropic effect via H-1 receptors.¹¹ Cardiac anaphylaxis with various types of AV block has been widely reported in the human literature.^25,26 Heightened vagal tone could have also been involved given the dog’s gastrointestinal signs related to anaphylaxis.

The dog of the present report did not have obvious cardiac sequelae after recovery from anaphylaxis. Given the diagnosis of trypanosomiasis, continued monitoring for development of arrhythmias, cardiomyopathy, and heart failure was warranted, but was declined. The present case highlights that trypanosomiasis can cause subclinical disease but increase the risks for development of malignant arrhythmias in the event of a cardiovascular insult such as anaphylaxis. Therefore, trypanosomiasis must always be considered in the differential diagnosis for dogs with malignant arrhythmias in endemic areas, even in the absence of cardiac structural abnormalities or failure. Furthermore, anaphylaxis should also be recognized as an important triggering factor for development of various types of arrhythmias.