John Bonagura United States
Myocardial diseases are a common cause of heart failure, arrhythmia, and cardiovascular mortality in the dog. The most common of the canine myocardial diseases represent “primary” disorders of the myocardium. These are manifested as idiopathic dilated cardiomyopathy (DCM), arrhythmogenic cardiomyopathy (ACM), or both problems. ACM is characterized by recurrent atrial arrhythmias, lone atrial fibrillation (AF), or by ventricular ectopia without obvious echocardiographic evidence of myocardial failure. DCM is typified initially by asymptomatic decreases in left ventricular ejection fraction (so called occult DCM) followed by progressive left ventricular dysfunction culminating in congestive heart failure (CHF). Sudden cardiac death can occur in either form. Most cases of cardiomyopathy are influenced by genetic factors, including breed, body size, and sex.
Aside from DCM and ACM, most other forms of cardiomyopathy are considered relatively rare in dogs. Persistent atrial standstill in Springer Spaniels and other canine breeds is diagnosed sporadically. Primary hypertrophic cardiomyopathy is rare in dogs but is a differential diagnosis for sudden death. Hypertrophic cardiomyopathy is also encountered with some regularity in mature Boston Terrier dogs. Secondary causes of canine myocardial disease include hypertrophy or injury from systemic hypertension, hypothyroidism, iatrogenic hyperthyroidism, catecholamines, doxorubicin, brain-heart syndrome, ischemia, Duchenne’s myopathy, and myocarditis (including Chagas disease). Chronic volume or pressure overloads (as with congenital shunts or chronic valvular disease) can progress to the “cardiomyopathy of overload,” wherein the ventricle is hypertrophied and myocardial function impaired. Cardiac tamponade, transient myocardial ischemia, and relentless supraventricular or ventricular tachycardias are causes of reversible myocardial failure.
The term “arrhythmogenic cardiomyopathy” (ACM) is a useful term that refers to recurrent or persistent arrhythmia in the setting of a normal left ventricular ejection fraction. While some dogs affected with ACM clearly go on to develop classic DCM, many do not, and in some, the key to clinical management is control of the cardiac arrhythmia. ACM is particularly common in the Boxer (and some English Bulldogs) where the term arrhythmogenic right ventricular cardiomyopathy (ARVC) is sometimes used to indicate the presumed origin of arrhythmia. The Doberman Pinscher is another breed that often manifests ventricular ectopics prior to the development of overt myocardial failure (DCM). Another common example is the Irish Wolfhound (and other giant breeds); these dogs are prone to atrial fibrillation (AF) without obvious impairment of LV contractility, a condition sometimes referred to as lone AF. Other atrial arrhythmias may be recognized in ACM including ectopic atrial tachycardia and atrial flutter.
ACM must be distinguished from other causes of cardiac arrhythmia such as an atrial tumor (hemangiosarcoma), electrolyte imbalance (hypokalemia), splenic tumor, or post-operative ventricular arrhythmia (probably caused by ischemia and reperfusion). Similarly, a medication history should be obtained to insure the arrhythmia is not caused, for example, by ongoing treatment for respiratory disease (using sympathomimetic airway dilators) or by therapy for hypothyroidism (excessive supplementation resulting in iatrogenic hyperthyroidism). Some breeds that are prone to DCM are also predisposed to hypothyroidism and may be receiving supplemental L-thyroxin. Successful management of ACM includes 1) assessing the rhythm disturbance using routine and ambulatory (Holter) ECG; 2) measuring LV ejection fraction by echocardiography; 3) reviewing relevant clinical signs; and 4) judging the clinical significance of the arrhythmia.
In dogs with lone AF, the Holter data provide insight about the daily heart rate and the exercise heart rate. Average daily heart rates that exceed 90–95/min or moderate-level exercise heart rates that exceed 250/min are reasonable grounds for slowing the heart rate response to AF. This can be done with a beta-blocker such as atenolol (6.25 to 25 mg PO q12h) or metoprolol (12.5 mg PO q12h in giant breeds). The initial dose of the beta-blocker should be low to prevent lethargy, but it can be titrated up over two to four weeks to achieve an appropriate average daily rate (generally in the range of 70 to 80/min). Digoxin can be prescribed for lone AF, but cardiac glycosides are less effective for controlling excessive exercise-related rates and are not recommended by the author unless there is congestive heart failure. Diltiazem (0.5 to 1.5 mg/kg PO q8h) is very effective in controlling heart rate, but does not confer the “cardioprotection” of beta-blockers should the arrhythmia represent occult DCM.
Grading the severity of ventricular arrhythmias in terms of relative risk for sudden death is more difficult. Clearly, the presence of clinical signs (collapse, syncope) is an indication to control ventricular tachycardia if the clinician is certain that a tachyarrhythmia is the basis for the spells. If uncertain, an event monitor (client activated ECG) should be prescribed and worn by the dog. The more common problem is when there are no overt clinical signs but frequent ventricular ectopic beats. Here the clinician must attempt to judge the seriousness of the arrhythmia. If the Holter ECG shows rapid runs of ventricular tachycardia (exceeding 225/min), frequent ectopics (such as more than 7,000 per 24 hour period), or “warning” arrhythmias (such as short-coupled PVC’s, or flutter-like runs of ventricular tachycardia), antiarrhythmic therapy is recommended.
Treatment depends in part on personal preference. For frequent single VPC/PVCs, a simple beta-blocker may be effective in controlling the rhythm (see doses above). For ventricular tachycardia, either sotalol (40 to 80 mg PO q12h for a large dog) or the combination of mexiletine (5–8 mg/kg q8h) plus a beta-blocker represent effective therapy for reducing the frequency of ventricular beats and runs. The value of these in preventing sudden cardiac death has not been proven however. In difficult to manage cases, amiodarone may be tried. Procainamide plus a beta-blocker is used by some, but appears to be less effective and more pro-arrhythmic. It should be emphasized that beta-blockers, sotalol, and amiodarone are negative inotropic drugs. Sotalol in particular is a class III drug with potent beta-blocker effects and it must be used with great care—if at all—in the setting of congestive heart failure or when LV ejection fraction is substantially depressed. In dogs with obvious CHF, mexiletine is the preferred treatment to control serious ventricular arrhythmias. Once CHF is treated (see below), the gradual upward titration of a beta-blocker may confer better control of the rhythm and protection against sudden death.
Dilated cardiomyopathy (DCM) is an idiopathic, genetic, or familial myocardial disease characterized by cardiac dilatation and reduced myocardial contractility. Histologic lesions include absence of inflammation, attenuated wavy fibers, loss of myocytes, and the presence of increased myocardial fibrosis. Coronary arteries are normal and the valves unremarkable, except in older dogs with concurrent mitral or tricuspid valve endocardiosis. Deficiency of metabolic substrates (such as L-carnitine or taurine) is found in a minority of dogs, but the exact cause and effect relationship between these substrates and DCM is incompletely understood. There is no published evidence for deficiency of co-enzyme Q10 in this disorder. The onset of myocardial failure and limited cardiac output is followed by an assault of neurohormones and cytokines released to support arterial blood pressure. However, neurohormonal activation is associated with further myocardial damage. The left ventricular ejection fraction continues to decrease, the heart dilates, and ventricular diastolic dysfunction can be recognized by detailed echocardiographic studies. Secondary atrioventricular valvular regurgitation often develops leading to murmur of mitral or tricuspid regurgitation. Renal retention of sodium and water combines with reduced left ventricular performance to produce CHF. Arrhythmias can occur at any time during the course of disease. Syncope, sudden cardiac death, or CHF are potential consequences of these events. Frequently, biventricular CHF is precipitated by development of AF in a dog with previously “compensated” DCM.
Dilated cardiomyopathy occurs most often in middle-aged, male, large and giant breed dogs, such as the Doberman Pinscher, Great Dane, and Irish Wolfhound, but DCM can affect dogs of any age and many other these breeds. Often males are predisposed or more likely to be affected at a young age. In addition to the large-breed dog, DCM is recognized regularly a variety of spaniel breeds, and the condition occurs sporadically in small canine breeds. The precise genetic basis for DCM has not been demonstrated. The four most common clinical presentations of DCM are 1) occult DCM; 2) cardiac arrhythmia (see above); 3) sudden cardiac death; and 4) congestive heart failure (CHF).
Occult DCM indicates an overtly healthy dog with echocardiographic evidence of systolic dysfunction by echocardiography. Most diagnoses are made when a breeder requests screening of an important dog or after a veterinary examination uncovers a murmur or arrhythmia. In most cases the “diagnosis” of occult DCM is based on a minor axis measure of LV systolic function (the shortening fraction). Values below 25% are considered suspicious in most laboratories, but there is no unanimity about one specific figure that indicates myocardial failure. This single linear approach can be questioned because larger dogs shorten relatively more in the apical to basilar direction and this motion is not assessed by the shortening fraction measure. Before rendering a diagnosis of occult DCM, the clinician should request more detailed echocardiographic measures of systolic function including LV short-axis shortening area, apical-to-basilar mitral annular motion, and volumetric estimates of LV ejection fraction using the method of discs or a prolate ellipsoid model. Serial examinations also can be helpful in establishing a downward trend in LV function. Holter ECG is a useful adjunct for establishing the diagnosis in breeds prone to DCM with cardiac arrhythmias. Most would consider >50 VPC/PVC’s per day abnormal. When the diagnosis of occult DCM is certain, cardioprotection should be considered. This can be initiated with an angiotensin converting enzyme inhibitor (ACEI) such as enalapril, benazepril, ramapril (ramipril), or quinapril given once daily. If persistent arrhythmias are evident, a beta-blocker or sotalol should also be considered (see above for doses).
Advanced cases of DCM are presented with exercise intolerance and clinical signs of CHF. There can be marked weight loss and cachexia. Syncope related to ventricular arrhythmia or neurocardiogenic syncope (inappropriate bradycardia and vasodilation) may be related by the owner. Clinical signs of left-sided CHF include tachypnea, respiratory distress, and coughing related to pulmonary edema. Right-sided CHF is characterized by jugular pulses and jugular venous distension, hepatomegaly, and ascites. Biventricular failure includes the above findings along with pleural effusion. Auscultation may reveal atrial and ventricular gallops, systolic murmurs, or arrhythmias. The arterial blood pressure usually is normal owing to vasoconstriction and neurohormonal activation, but will be decreased in profound DCM with cardiogenic shock. The intensity of the first heart sound and strength of the arterial pulse are often diminished, indicating reduced LV contractility and stroke volume. Crackles of pulmonary edema or a pleural fluid line may be evident.
Laboratory studies support the diagnosis in advanced cases of DCM. The EKG may demonstrate abnormalities typical of cardiomegaly (wide or tall P-waves; wide or increased amplitude QRS complexes) or myocardial disease (wide QRS, slurred R-wave descent, and ST-segment coving). One or more of the aforementioned cardiac arrhythmias may be evident, though an ambulatory EKG is needed to assess the frequency of ventricular ectopic rhythms. The signal averaged EKG may demonstrate late potentials indicating increased risk for ventricular fibrillation. Thoracic radiography reveals cardiomegaly and may demonstrate typical radiographic features of heart failure. The echocardiogram shows ventricular dilation, reduced left ventricular shortening fraction, increased E-point to septal separation, decreased wall excursion, left atrial dilation and variably right-sided cardiomegaly. Doppler evidence of mitral regurgitation and tricuspid regurgitation, pulmonary hypertension, and diastolic ventricular dysfunction are common. Routine laboratory tests are usually normal or reflect intercurrent disease, consequences of CHF, or complications of CHF therapy. Specialized blood tests for L-carnitine or taurine may be performed in selected cases.
Initial hospital therapy of CHF caused by DCM includes diuresis with furosemide (2–4 mg/kg IV, IM q6-8h), supplemental oxygen, nitroglycerin ointment (1–1.5 inches for a large breed dog q12h), and rest. Life-threatening pulmonary edema can be managed with furosemide and infusion of sodium nitroprusside (0.5–2.5 mcg/kg/min) with careful attention paid to arterial blood pressure (titrate the infusion to a systolic value of 85 to 90 mm Hg). Thoracocentesis is indicated for moderate to large pleural effusions. When there is CHF with systemic hypotension, the treatment should be furosemide, oxygen, and dobutamine (2.5 to 10 mcg/kg/min). Dobutamine can have relatively long-term benefits and is continued for at least two days, at which point the drug is tapered over a 6–12 hour period while assessing blood pressure. In the setting of hypotension, vasodilators are avoided until the pressure is stabilized by dobutamine for at least two hours after which therapy with either sodium nitroprusside or an ACEI can be initiated (see below). In dogs with atrial fibrillation, digoxin (0.005 mg/kg PO q12h) is prescribed to control the ventricular rate response.
Home therapy for CHF caused by DCM includes furosemide, an ACE-inhibitor, digoxin, and sodium-restricted diet. Fluid retention is controlled with furosemide (2–4 mg/kg PO q8-12h) and sodium restriction if possible. Digoxin therapy is initiated unless there is a contraindication (moderate renal failure, complicated ventricular ectopics). An ACEI is prescribed for once daily use (with a typical dose of 0.5 mg/kg PO for enalapril or benazepril), and the dose increased to twice daily after one or two weeks of home care. Where available, pimobendan (a phosphodiesterase inhibitor-calcium sensitizing inotropic drug with vasodilating properties) should be considered based on limited but promising clinical studies. Spironolactone (12.5 to 25 mg PO q12h in a large dog) may be added to block the cardiotoxic effects of aldosterone and impede sodium retention in the distal nephron. A beta-blocker may be considered to blunt the cardiotoxic effects of the sympathetic nervous system; however, heart failure must be well controlled first. The beta-blocker of choice in human patients is carvedilol. This drug is both a beta-blocker and alpha-adrenergic blocker (which helps to reduce the afterload on the left ventricle). Carvedilol also had anti-oxidant properties that may benefit the myocardium. Unfortunately, the prescription drug (Coreg) is expensive. Dosing can be difficult even in large dogs that may not tolerate the negative inotropy of any beta-blocker. Thus, low initial dosages are mandatory (start with ¼ to ½ of a 3.125 mg carvedilol tablet q12h). Drugs such as propranolol (0.1–0.25 mg/kg PO q8-12h) are easier to dose, but have the disadvantage of greater “inverse agonism” (inactivating the active state of beta receptors) and causing greater negative inotropy. Metoprolol long acting (3–12.5 mg q12h) has been studied in experimental canine heart failure, but the drug is difficult to dose at less than 12.5 mg, which is too large for an initial dose. While there are clear theoretical benefits of beta-blockers in canine DCM, one’s practical ability to initiate and maintain treatment may be very limited and CHF can worsen (often with pleural effusion). Certainly, when AF complicates CHF, either a beta-blocker or diltiazem (0.25 to 1.0 mg/kg PO q8h) is prescribed to control ventricular rate. Nutraceuticals (taurine or L-carnitine) are used empirically in selected cases. When DCM occurs in spaniels or small breed dogs, taurine supplementation (500 mg q12h) is recommended. Fish oil supplements containing omega-3 fatty acids may improve appetite and reduce cardiac cachexia (EPA–30 to 40 mg/kg PO q24h; DHA 20 to 25 mg/kg PO q24h). Serious ventricular arrhythmias in the setting of CHF are managed with mexiletine (5–8 mg/kg q8h) plus a low dose beta-blocker. Sotalol can be tried in larger dogs (40 mg q12h) but can worsen CHF. A Holter EKG should be used to assess therapy.
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