Dilated Cardiomyopathy and Sinoatrial Dysfunction in an Estrela Mountain Dog

Introduction

Dilated cardiomyopathy (DCM) is a primary myocardial disorder characterized by reduced contractility and dilation of the left or both ventricles. DCM may be either familial or of unknown etiology.^1,2 Sinoatrial dysfunction (SAD) is an electrophysiologic abnormality characterized by disorders of sinus node automaticity and of sinoatrial conduction. SAD refers to a broad array of abnormalities in sinus node and atrial impulse formation and propagation, and is often associated with atrioventricular (AV) conduction disturbances.^3,4

The Estrela mountain dog is a large-breed dog with a known predisposition to DCM.^5,6 The natural history of DCM is not well known in most breeds, with the exception of Doberman pinscher dogs in which a very long subclinical or occult stage has been described.¹ In the occult stage, dogs show evidence of left ventricular enlargement and/or ventricular premature contractions on resting and/or ambulatory electrocardiography (ECG).^1,7 This occult phase can last as long as 2–4 yr.¹

This report describes the occult phase of a young Estrela mountain dog with DCM in which SAD was documented in addition to the ventricular dilation. This dog is part of a group of Estrela mountain dogs with DCM with similar disease characteristics who have been followed by the authors.

Case Report

A 1 yr old intact male Estrela mountain dog weighing 48 kg presented to the Hospital Veterinário do Porto, Portugal, in June 2006 as part of a screening program for DCM. Although there was no history of cardiac-related symptoms in this dog, there was a history of DCM-related deaths in the family, including the sire. No abnormalities were found on physical examination. Blood pressure was measured and an ECG and echocardiography were performed. Mean pressure values, measured using an oscillometry technique, were within normal limits for the breed.⁵ A 12-lead resting ECG was performed as previously described.⁸ An irregular sinus rhythm was observed with a rate of 80 beats/min with several episodes of sinus arrest or sinoatrial block with ventricular escape beats (Figure 1). The ECG measurements were within normal canine electrocardiographic values.⁹ A complete echocardiographic examination was performed, and a diagnosis of dilated cardiomyopathy was then established (according to the guidelines for the diagnosis of canine idiopathic dilated cardiomyopathy), taking into account the reference values for the breed (Table 1).^2,5

TABLE 1 Echocardiographic Measurements for the Estrela Mountain Dog Described in This Report and Reference Values for the Breed⁵

EF, ejection fraction; EPSS, E point to septal separation; ESVI, end-systolic volume index; FS, fractional shortening; IVSd, interventricular septal thickness at end-diastole; IVSs interventricular septal thickness at end-systole; LA/Ao, left atrium aorta index; LVIDd, left ventricular internal dimension at end-diastole; LVIDs, left ventricular internal dimension at end-systole; LVPWd, left ventricular posterior wall thickness at end-diastole; LVPWs, left ventricular posterior wall thickness at end-diastole; MV E/A, mitral valve E/A index; SD, standard deviation.

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A 24 hr ambulatory ECG was performed using a three channel digital recorder. A patient diary was also prepared during the exam. During the 24 hr ECG, the minimum heart rate (HR) was 31 beats/min and the maximum HR (in supraventricular tachycardia) was 222 beats/min. The software was set to detect pauses of >2 sec in duration. In total, 103 pauses were detected. The longest was 4.4 sec at 8:21:19 AM, which coincided with a period of activity, according to the patient diary. During the exam, 2,600 ventricular escape beats associated with pauses were detected, and 28 runs of a ventricular escape rhythm were also detected. The HR during this rhythm ranged between 36 beats/min and 53 beats/min, with a maximum duration of 9.1 sec/six beats. Several periods of alternating bradycardia and supraventricular tachycardia were observed (Figure 2). Analyzing the histograms for HR and ventricular escape beats (Figures 3, 4) and comparing it to the patient diary, it was concluded that there were no circadian variation or relation to the activity.

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An atropine response test (0.04 mg/kg subcutaneous) was performed to test for sinoatrial node function. The HR failed to increase 30 min after atropine administration. A multistage exercise test was performed by walking the dog on a motorized treadmill at three different speeds (0.5, 1.0, and 1.5 m/sec) for 3 min at each speed as previously reported.¹⁰ The ECG was monitored using a Holter recorder and analyzed retrospectively. The HR ranged between 85 beats/min and 111 beats/min during the test.

To better clarify the changes seen on the ECG, an electrophysiologic (EP) study was performed. The dog was premedicated with butorphanol^a and diazepam^b. Anesthesia was induced with propofol^c and maintained with isoflurane^d, which was a similar protocol used to assess reference values.¹¹ Three catheter introducer sheaths were placed in the right external jugular vein. With the dog in dorsal recumbency and using fluoroscopic and intracardiac electrogram guidance, an octapolar electrode catheter was advanced into the right external jugular vein and cranial vena cava to the coronary sinus. A quadripolar catheter was used to record the His bundle potential, and a bipolar catheter was placed in the right ventricular apex. Surface and intracardiac electrograms were recorded using an EP tracer system^e. The following standard measurements were then obtained: sinus cycle length; the interval of time between successive atrial impulses; p wave-to-atrial interval (representing the intra-atrial conduction interval and approximating the conduction time from the sinus node to the AV node); atrio-to-His interval (AH; representing the conduction time through the AV node); and His-to-ventricular interval (representing the conduction time through the His-Purkinje system). The p wave-to-atrial interval, AH, and His-Purkinje system are the three basic components of the PR interval.¹² Additionally, the sinoatrial conduction time was measured to assess conduction of the sinoatrial nodal impulse to the surrounding atrial tissue, sinus node recovery time (SNRT), the interval measured from the last paced complex to the first spontaneous complex after the cessation of pacing, corrected SNRT (to exclude the influence of sinus cycle length on SNRT), and AV nodal Wenckebach point (the pacing cycle length at which second-degree AV block develops after a gradually increasing the AH). The results and reference values have been presented in Table 2.

TABLE 2 Electrophysiologic Measurements and Reference Values¹¹

AH, atrio-to-His interval; CSNRT, corrected sinus node recovery time; HV, His-to-ventricular interval; PA, p wave-to-atrial interval; SACT, sinoatrial conduction time; SCL, sinus cycle length; SNRT, sinus node recovery time; WP, atrioventricular nodal Wenckebach point.

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With the electrode in the coronary sinus, atrial fibrillation with a slow ventricular response (80 beats/min) was induced and not spontaneously terminated. It was converted into sinus rhythm using direct current cardioversion of 100 Joules.

The dog has remained asymptomatic for 4 years following initial evaluation.

Discussion

Screening Estrela mountain dogs for DCM prior to breeding, similar to the situation with Doberman pinschers, can be challenging because the occult phase can be quite long. Echocardiography and ECG are helpful tools in the identification of this phase, and the knowledge of changes in these tests for a specific breed is important to create the criteria on which to base a diagnosis.²

The dog in this report is part of a screening program for DCM in this breed. This form of DCM is consistent with previous work by the authors. DCM has characteristic histopathologic changes in which both “attenuated wavy fibers” and “fatty infiltration/fibrosis” are observed.¹³ Historically, two distinct histologic forms of DCM (i.e., “fatty infiltration-degenerative” and “attenuated wavy fibre” types) are usually associated with different breeds of dogs, each breed having a specific histologic type of DCM.^2,14–19

The Doberman pinscher is the breed in which the natural history of DCM, including its occult phase, is best studied and described.^1,7,20 This phase can last as long as 2–4 yr, and dogs show evidence of left ventricular enlargement and/or the presence of premature ventricular contractions on resting or ambulatory ECG.^1,7,20 There are few descriptions of electrocardiographic data of the occult phase in large and giant breeds of dogs.^1,2 In Irish wolfhounds, atrial fibrillation may be an early indicator of the presence of myocardial disease preceding echocardiographic signs of DCM.^2,21 In Irish wolfhounds, atrial fibrillation is the most common rhythm disturbance, but a wide variety of ventricular and supraventricular arrhythmias and conduction disorders (such as first-degree AV block) can be observed in dogs without echocardiographic evidence of DCM.²¹

Echocardiography is essential to establish a diagnosis of DCM and exclude other causes of heart disease.²² In the present case, the echocardiogram fulfills the criteria for the diagnosis of DCM (Table 1).²

The electrocardiogram and subsequent Holter examination were compatible with SAD given the observation of marked sinus bradycardia, sinus arrest/sinoatrial block, escape rhythms, and bradycardia/tachycardia syndrome.^23,24 A correlation of these changes with an activity log was important because prolonged sinus pauses up to 5 sec and bradycardia are expected when the dog is sleeping, but inappropriate if occurring during activity.²⁵ The atropine response test and exercise testing aided in differentiating intrinsic conduction abnormalities from vagal origin SAD that can be observed in normal healthy animals.^24,26

The only EP value that exceeded the reference range was AH (132 msec; reference range, 64–118 msec), suggesting a delay in the conduction time from the low right atrium near the AV node to the His bundle.^22,27 The SNRT and corrected SNRT were used to evaluate sinoatrial nodal function and the automaticity of the sinus node. In dogs, it is suggested that a prolonged SNRT indicates sinus node dysfunction.²³ The SNRT was within the normal published reference range. A wide variation in reference ranges for tests of sinoatrial nodal function are typical of dogs as well as humans, and a diagnosis of SAD could not be excluded with a test within the reference range.¹¹ In humans, both the sensitivity and specificity of sinoatrial nodal function tests are known to be approximately 70%.²⁸ Furthermore, variance in EP reference ranges in dogs, as in people, can be expected for different age groups and different body weights.¹¹ The reference values used herein were taken from adult dogs weighing between 12 kg and 25 kg. It is unclear whether this data can be extrapolated to either younger dogs or dogs outside this weight range, which probably leads to the need for further studies to establish EP reference values.

EP studies are indicated in people with signs of SAD for whom noninvasive approaches have provided no explanations for the symptoms.^28,29 In the present case report, resting and ambulatory ECG demonstrated the existence of sinus node disease in an asymptomatic dog. The Holter activity log analysis, exercise, and atropine testing demonstrated the intrinsic nature of the conduction abnormalities. The EP study did not provide additional proof of SAD, but it did provide information on abnormal AV conduction, reflected by a prolonged AH interval. This finding is consistent with the current knowledge that many dogs with SAD, as in humans, also have coexisting abnormalities of the AV junction.^23,24,29,30 Additionally, AH prolongation can be associated with an increased incidence of organic heart disease and myocardial dysfunction as AH prolongation has been observed in people with chronic bundle branch block.³¹

This case report describes a case of SAD associated with DCM in an Estrela mountain dog. Given the fact that the authors have observed other related dogs affected in the same way, it is possible that the SAD and DCM are related. Although this correlation has never been reported in veterinary medicine, studies in humans report novel genes for DCM encoding cardiac ion channels, and there are several reports in which DCM is associated with conduction defects.^32,33 Ion channel mutations in people, especially in the SCN5A gene, have been identified as a genetic risk factor for rhythmic disorders (such as long-QT syndrome and Brugada syndrome) and are attributed to electric abnormalities without myocardial damage.^34,35 More recent data suggests a possible pathogenic role of cardiac sodium channel defects in myocardial structural abnormalities, leading to hereditary forms of DCM associated with conduction disorders such as sinus node dysfunction and AV block.^32,33,36 Furthermore, studies in mice established a functional connection between loss of sodium channel function and DCM.³⁷

Recently, the search for candidate genes responsible for DCM in dogs has been directed toward genes encoding structural proteins of the contractile apparatus and cytoskeleton.^38–41 However, recent data from human medicine suggest that DCM may result not only from structural changes in the myocytes, but also from altered ion homeostasis, implicating mutations of genes encoding cardiac ion channels.^32,33,36,37 Furthermore, congenitally deficient nodal tissue is reported in children, which is also associated with SCN5A mutations.⁴² Finally, degenerative fibrosis, atrophy, infiltrative processes, fatty replacement, arteritis, and myocarditis have all been found to play a role in sinus node disorders.⁴³

Conclusion

This case report raised the hypothesis that, as in people, DCM and SAD could be correlated in Estrela mountain dog. Long-term follow-up of more dogs and the study of affected families with similar disease characteristics are now required to better characterize DCM in the Estrela mountain dog.