Veterinary Medicine

Dilated cardiomyopathy in the cat

The aetiology of primary dilated cardiomyopathy in the cat is unknown. Recent work has indicated a close association between dietary taurine deficiency and dilated cardiomyopathy. In the cat, taurine is an essential amino acid which is required for the conjugation of bile acids. The premise that taurine deficiency is one of the causative factors in the pathogenesis of dilated cardiomyopathy is based on the fact that many cats on taurine-deficient diets develop myocardial failure which can be reversed with taurine supplementation.

However, not all cats on taurine-depleted diets develop dilated cardiomyopathy and some which do develop cardiomyopathy fail to respond to taurine supplementation. About 38% of cats with dilated cardiomyopathy in one study failed to respond to taurine supplementation and died within the first 30 days of treatment. Hypothermia and thromboembolism were found to increase the risk of early death.

It is also known that cats on apparently adequate diets can nevertheless become taurine deficient. The minimal concentration of taurine in the diet required to prevent signs of deficiency varies with the type of diet. For example, it has been shown that much higher concentrations (2000-2500 mg taurine / kg dry matter) of taurine are required in canned diets compared to dry cat foods since heating during the canning process produces products which increase the enterohepatic loss of taurine. Low plasma taurine levels have been reported in cats fed a taurine replete but potassium depleted diet containing 0.8% ammonium chloride as a urinary acidifier suggesting a possible association between taurine and potassium balance in cats. Dietary acidification exacerbates potassium depletion in cats by decreasing gastrointestinal absorption of potassium.

It has been suggested therefore that the aetiology of feline dilated cardiomyopathy, like that of dilated cardiomyopathy in dogs, is multifactorial. There is some evidence to show that genetic factors may play a role in feline dilated cardiomyopathy. Burmese, Siamese and Abyssinian cats appear predisposed. The incidence of dilated cardiomyopathy is higher in young to middle-aged cats; the evidence for a sex predilection is equivocal).


Impairment in myocardial contractility leads to systolic dysfunction and increased end-diastolic pressures. Progressive dilatation of the ventricles results in distortion of the atrioventricular valve apparatus and mitral regurgitation which, together with the reduction in myocardial contractility, contributes to the reduction in stroke volume and decreased cardiac output.

Clinical signs of Dilated cardiomyopathy

The clinical signs may be gradual in onset and are often rather vague (lethargy, reduced activity and decreased appetite). Many of the presenting signs are similar to those of hypertrophic cardiomyopathy making differentiation between the two diseases on a clinical basis difficult. Cats which are dyspnocic may be dehydrated and hypothermic with weak femoral pulses. There may be obvious pallor or cyanosis of the mucosae with a prolonged capillary refill time. Increased respiratory crackles in association with a gallop rhythm and systolic murmur are common findings; the presence of a large volume of pleural fluid may result in muffled heart sounds. Less frequently there is also evidence of right-sided failure (jugular distension, and hepatomegaly); ascites is a rare finding.


The electrocardiographic changes do not help differentiate dilated cardiomyopathy from the hypertrophic form of the disease. Some cats remain in a relatively slow sinus rhythm. Tall R waves and wide P waves and QRS complexes may be apparent in Lead II.

Arrhythmias, especially ventricular premature complexes, have been recorded in more than 50% of cases. The mean electrical axis is often within normal limits.

Radiographic findings

Thoracic radiographs typically show evidence of generalized cardiomegaly; enlargement of the-left atrium may be particularly marked. The cardiac silhouette is often obscured by the presence of a bilateral pleural effusion. Pulmonary venous congestion and oedema may be present but these changes are usually mild and are often masked by the presence of fluid in the pleural space. The caudal vena cava is often dilated and there may be evidence of hepatomegaly.


Echocardiography offers the most reliable means of differentiating dilated cardiomyopathy from hypertrophic cardiomyopathy. The interventricular septum and left ventricular free wall appear thin and poorly contractile with a marked reduction in fractional shortening. Both ventricles and the left atrium appear dilated and left ventricular end-diastolic and end-systolic internal dimensions are increased.

Laboratory findings

Normal plasma taurine levels are greater than 60 nmol l-1 ; most cats with dilated cardiomyopathy have plasma taurine concentrations less than 20 nmol l-1 and often less than 10 nmol l-1. Taurine-defielent cats with thromboembolism may have slightly higher plasma taurine concentrations due to reperfusion hyperkalaemia. Whole blood taurine has been reported to be less sensitive to acute changes in taurine intake and provides a better indication of long-term taurine intake. Whole blood taurine concentrations greater than 280 nmol l-1 are considered adequate.

Prerenal azotaemia is a common finding in cats with dilated cardiomyopathy because of reduced renal perfusion. The pleural effusion which develops with feline dilated cardiomyopathy is typically a serosanguineous modified transudate; true chylous effusions have been reported in association with right heart failure.


Non-selective angiocardiography can be used to demonstrate dilatation of all cardiac chambers. The slow circulation time in cats with dilated cardiomyopathy increases the risk of thromboembolus formation during this procedure and decompensated cases should be stabilized beforehand.

Dilated cardiomyopathy: Treatment

Cats which are severely dyspnoeic should be given oxygen, kept warm and placed in a cage. Dyspnoeic animals, particularly those with suspected pleural effusion, should be handled with care and should not be placed in dorsal or lateral recumbency for radiography. A dorsoventral radiograph taken with the animal resting in sternal recumbency is usually sufficient to confirm the presence of pleural fluid. Thoracocentesis should be attempted before a more detailed radiographic examination is performed. Other therapeutic strategics are summarized below.

Digoxin improves myocardial contractility in some but not all cats with dilated cardiomyopathy and it has been suggested that the drug may act synergistically with taurine in this respect.The liquid form of the drug is unpalatable and is generally not well tolerated. There is considerable individual variation in the way in which cats respond to digoxin. The maintenance oral dose is 0.01 mg kg-1 every 48 h for an average 3-4 kg cat which is less than one quarter of a 62.5 μg tablet every other day. Cats with dilated cardiomyopathy are more susceptible to digoxin toxicity and tend to show toxic signs when the plasma concentration of digoxin is approximately 50% of the level which would be considered toxic in a normal healthy cat. Approximately 50% of cats given 0.01 mg kg-1 body weight every 48 h show signs of toxicity.

Other positive inotropic agents such as dopamine and dobutamine must be given by constant slow intravenous infusion and are, therefore, not used as extensively. Both drugs can be given at a rate of 1-5 μg kg-1 body weight min-1 ; with dobutamine, seizures have been reported with infusion rates as low as 5 μg kg-1 min-1 in cats.

Frusemide (initially 1.0 mg kg-1 body weight intravenously twice daily; for maintenance 1-2 mg kg-1 body weight per os once or twice daily)

Mixed arteriovenous vasodilators such as captopril (3.12-6.25 mg kg-1 body weight per os twice or three times daily; this dose equates to approximately one-eighth to one quarter of a 25 mg tablet) or venodilators such as 2% nitroglycerine ointment (1/8-1/4 inch applied three times daily to the inside of the pinna) can be given although the beneficial effects of these drugs have yet to be evaluated fully in cats with dilated cardiomyopathy. They should not be given to cats with cardiogenic shock since they may potentiate the fall in cardiac output especially if used in conjunction with diuretic agents.

Animals which are severely hydrated may require intravenous or subcutaneous fluid therapy, for example 0.45% saline with 2.5% dextrose solution may help combat the effects of circulatory failure. The recommended rate of infusion is 25-35 ml kg-1 body weight day-1 given in two or three divided doses. Care should be taken so that the rate of infusion optimizes cardiac output but minimizes the risk of exacerbating pulmonary oedema or a pleural effusion.

Aspirin (25 mg kg-1 body weight every 72 h).

Taurine supplementation (250-500 mg per os twice daily) may result in a dramatic clinical improvement within 1-2 weeks when dilated cardiomyopathy is associated with taurine deficiency although cehocardiographic evidence of improved cardiac performance is usually not evident until after at least three weeks of treatment.

Sodium restricted diet.


The prognosis for cats which fail to resond to taurine therapy is poor. About 93% of early deaths occur within the first two weeks; few survive longer than one month. Taurine supplementation can eventually be discontinued if adequate taurine intake is provided for in the food.

Veterinary Medicine

Hypertrophic cardiomyopathy in the cat

The incidence of hypertrophic cardiomyopathy (HCM) is higher in the cat than it is in the dog. hypertrophic cardiomyopathy can be classified as primary or secondary. The aetiology of the primary or idiopathic form is unknown. A recent survey of 74 cases of hypertrophic cardiomyopathy showed no apparent breed predilection ; others have suggested that the Persian breed may be predisposed. The disease rarely occurs in the Siamese. Burmese and Abyssinian breeds in which there is a much higher incidence of dilated cardiomyopathy. Secondary hypertrophic cardiomyopathy most commonly occurs in association with hyperthyroidism.

Idiopathic hypertrophic cardiomyopathy typically occurs in young to middle-aged cats (mean age 6,5 years) and males are more commonly affected.


Hypertrophic cardiomyopathy is characterized by symmetrical hypertrophy of the interventricular septum and left ventricular free wall. Occasionally there may be evidence of left ventricular outflow obstruction especially if there is disproportionate hypertrophy of the septum. Partial aortic outflow obstruction may also be caused by anterior motion of the mitral valve during early systole but this appears to be a rare occurrence in feline hypertrophic cardiomyopathy. Indeed, echocardiographic studies have shown that most cats with hypertrophic cardiomyopathy do not have left ventricular outflow gradients and it appears therefore that obstructive hypertrophic cardiomyopathy, as occurs in dogs, is rare in cats.

Left ventricular hypertrophy results in decreased myocardial compliance, interference with normal diastolic filling due to impaired myocardial relaxation, and an increase in left ventricular end-diastolic pressure (despite a normal or often reduced end-diastolic volume). Decreased myocardial compliance may be aggravated by focal or diffuse endocardial fibrous tissue deposition. Pressure overload within the left ventricle may also be associated with mitral valve dysfunction and regurgitation leading to left atrial enlargement.

The decrease in stroke volume ultimately leads to a reduction in cardiac output and decreased coronary perfusion resulting in myocardial ischaemia. Abnormal myocardial handling of calcium may be a factor in the pathogenesis of hypertrophic cardiomyopathy (an increase in intracellular calcium inhibits complete myocardial relaxation which may explain why calcium blocking drugs have been shown to improve diastolic function significantly in affected cats.

More recently, excessive circulating levels of growth hormone has been implicated in the pathogenesis of hypertrophic cardiomyopathy. Cats with acromegaly due to functional pituitary tumours have hypertrophic cardiomyopathy (Q). It has also been shown that non-acromegalic cats with hypertrophic cardiomyopathy have significantly increased levels of growth hormone compared to normal cats and cats with other forms of cardiac disease but whether this is cause or effect is not clear.

Hypertrophic cardiomyopathy: Clinical signs

Recent studies have demonstrated the heterogeneity of feline hypertrophic cardiomyopathy with regard to the wide spectrum of clinical, electrocardiographic, radiographic and echocardiographic features of the disease. Some cases of hypertrophic cardiomyopathy remain asymptomatic until the cat is stressed. The clinical signs of hypertrophic cardiomyopathy are typically those of left-sided congestive heart failure. Bright and others showed that 61 % of cats with hypertrophic cardiomyopathy had a history of respiratory distress characterized by the acute onset of dyspnoea progressing to mouth breathing. Affected cats become lethargic, anorexic and may cough. Occasionally heart sounds may be muffled due to the presence of pleural or pericardial fluid, Clinical examination may reveal diffuse pulmonary crackles and the presence of a gallop rhythm and / or systolic murmur. Other more variable signs include prolonged capillary refill time and pallor or cyanosis of the tongue and mucous membranes- Animals showing severe signs of cardiac failure are often hypothermic with weak femoral pulses. The increased tendency towards thrombus formation may result in acute onset of hindlimb (less frequently forelimb) paralysis or lameness with cold limb extremities (see section on arterial thromboembolism).


Almost 70% of cases may be expected to have an abnormal ECG. Abnormalities reported include increased amplitude and width of P and R waves (P waves >0.04 s and >0,2 mV; QRS complexes >0.04 s and R waves >0.9 mV in lead II), arrhythmias (atrial or ventricular premature contractions) and conduction disturbances. Left anterior fascicular bundle branch block, with deep S waves in leads 1, 11 and 111 and left axis deviation, is particularly common.

Radiographic findings

Radiographic abnormalities consisting of mild to moderate left atrial and left ventricular enlargement or biventricular enlargement with evidence of pulmonary venous congestion and / or oedema are present in more than 80% of cases. Biventricular enlargement may lead to elevation of the trachea and increased sternal contact and, on the dorsoventral view, the enlarged atria may result in a ‘valentine-shaped’ heart. Occasionally there may also be radiographic signs of right heart failure (right ventricular enlargement, hepatomegaly and ascites.


Hypertrophic cardiomyopathy is characterized by symmetric or less frequently asymmetric hypertrophy of the inter-ventricular septum and left ventricular free wall, and enlarged hypertrophied papillary muscles which contribute to a marked reduction in left ventricular internal dimensions. Most cases show evidence of a moderate degree of left atrial dilation and fractional shortening is usually normal or increased. Occasionally there is systolic anterior motion of the septal mitral valve leaflet and Doppler studies may show mitral regurgitation. Mild pericardial effusion may be evident.


With the increased use of ultrasound angiocardiography is rarely required. In the absence of ultrasound facilities, non-selective angiocardiography (injection of the contrast agent via the jugular vein) can be used to demonstrate the hypertrophied left ventricle and papillary muscles and regurgitation of contrast into the dilated left atrium. Circulation time is usually normal.

Prognosis of Hypertrophic cardiomyopathy

The prognosis for hypertrophic cardiomyopathy is guarded and other causes of left ventricular hypertrophy such as systemic hypertension, hyperthyroidism, acromegaly, chronic anaemia and congenital subaortic stenosis (rare in the cat) should be excluded. Plasma T3 and T4 concentrations should always be determined even when no thyroid nodules can be palpated in the neck.

Hypertrophic cardiomyopathy: Treatment

Cats presented with severe respiratory distress should be given oxygen and confined to a cage in the first instance. Initially frusemide may be given intravenously or intramuscularly (1-2 mg kg-1 body weight); thereafter it may be given orally at a dose rate of 1 mg kg-1 body weight two or three times daily. One of the main aims of therapy should be to reduce the heart rare to less than ISO beats per minute in order to improve cardiac filling.

Diltiazem not only decreases the heart rate in cats with hypertrophic cardiomyopathy but increases myocardial relaxation, decreases myocardial oxygen demand and dilates the coronary vasculature. It has minimal negative inotropic and peripheral vasodilating properties compared to other calcium blocking agents such as verapamil. A dose of 1.75-2.4 mg kg-1 body weight per os three times daily (mean effective dose 1.78 mg kg-1) has been shown to effectively reduce pulmonary congestion and improve left ventricular filling with no apparent side effects.

Recent work has shown that the survival times of cats with hypertrophic cardiomyopathy may be prolonged with the use of calcium Mocking agents such as diltiazem. About 94% of cats in one study receiving diltiazem survived longer than 6 months. Cats which show no clinical signs on initial presentation and those with heart rates less than 200 beats per minute survive significantly longer than do cats with emboli or congestive heart failure, 60% of which fail to survive 6 months.

Beta-blocking drugs such as propranolol (2,5-5,0 mg per os twice or three limes daily) slow the heart rate and improve diastolic filling. Propranolol is the antidysrhythmic drug of choice for cats but its effects on myocardial compliance in cases of feline hypertrophic cardiomyopathy have not been documented.

Although vasodilators are generally contra-indicated in cats with hypertrophic cardiomyopathy, captopril (3.12-6.20 mg twice or three times daily) may be useful In cases with severe mitral regurgitate on and signs of refractory congestive heart failure.

The administration of digoxin is contraindicated in cats with hypertrophic cardiomyopathy since myocardial contractility is often normal or increased. Aspirin (25 mg kg-1 body weight every 72 h) should be given to minimize the risk of throntboembolic disease although there is no evidence to date to suggest that aspirin, if given prophylactically, decreases the incidence of arterial thrombosis in cats with hypertrophic cardiomyopathy.

Veterinary Medicine

Positive inotropic agents

An ideal positive inotropic agent should increase the force of contraction of cardiac muscle at a given degree of end-diastolic stretch without reducing efficiency of energy use, increasing the heart rate or predisposing to cardiac arrhythmias. The drug should also lack vasoconstrictor action on peripheral blood vessels.

Drugs which enhance myocardial intracellular cyclic AMP concentration

Beta-adrenergic agonists and phosphodiesterase type III / IV inhibitors will both raise intracellular cyclic AMP and increase myocardial contractility. The synthetic catecholamine, dobutamine is the beta-adrenoceptor agonist of choice since it has selective action on beta-adrenoceptors and at dose rates which increase the force of contraction (3-7 μg kg-1 min-1), it has minimal effects on heart rate and no vasoconstrictor effects. It is used in the intensive care of severe myocardial systolic failure. It is rapidly taken up and metabolized by the tissues and has to be given by continuous intravenous infusion, the rate of which should be accurately controlled by an infusion pump. Continuous ECG monitoring is required to detect increases in heart rate and the onset of arrhythmias which are indicative of toxicity. Some studies in human medicine have suggested long-term beneficial effects even following brief dobutamine infusions. Similar studies have not been reported in veterinary medicine and the cost of the drug may be prohibitive for many patients.

The bypyridine compounds amrinone and milrinone (phosphodiesterase type III / IV inhibitors) were heralded as having great promise on their introduction, being potent positive inotropes with little effect on heart rate and possessing mild arteriolar vasodilator activity. Indeed, initial studies of the use of milrinone in dogs with systolic failure (which is orally active) proved promising. Unfortunately, no placebo-controlled trials have been performed in veterinary medicine and human studies have shown a detrimental effect of milrinone on long-term survival in patients with chronic congestive heart failure. Such findings cast serious doubt on the future of such drugs. Indeed, it has been suggested that any drug which produces its positive inotropic effects by raising cyclic AMP in the myocardium will have long-term detrimental effects in the same way as chronic exposure of the myocardium to high concentrations of catecholamines is thought to be toxic.

Cardiac glycosides

Controversy over the use of this group of drugs in the management of heart failure has been present in the literature of both human and veterinary medicine for many years, yet their popularity among clinicians survives. Most would agree that the primary indication for cardiac glycosides is in the management of supraventricular tachycardia, particularly where this co-exists with systolic myocardial dysfunction, as is often the case in dilated cardiomyopathy in dogs. The controversy surrounds their use in heart failure patients which are in normal sinus rhythm and results of large-scale controlled trials in human medicine are only beginning to be reported.

The classical actions of cardiac glycosides on the failing heart are to increase the force of contraction of the heart muscle and decrease the heart rate via a number of both central and peripheral effects which result in increased vagal tone to the heart. In addition, other reflex effects occur which inhibit both sympathetic nerve and renin-angiotensin system activity. The ability of the drugs to increase the sensitivity of cardiac and arterial baroreceptors so that they respond to lower pressures leading to a reduction in sympathetic tone may underlie these beneficial circulatory effects which are now thought to occur independently of any positive inotropic action. These effects give sound reasons for employing cardiac glycosides in heart failure patients where systolic muscle function is not affected (such as valvular heart disease) although alternative means of achieving these effects now exist (for example ACE inhibitors).

Digoxin is the only cardiac glycoside which currently is readily available for use by the veterinary practitioner. The narrow therapeutic index of glycosides means that the digoxin dosage should be accurately calculated for each animal. In dogs, less than 20 kg a dose of 0.005-0.01 mg kg-1 bid is recommended whereas dogs greater than 20 kg in weight should receive 0.22 mg m-2 bid (a total dose of 0,25 mg bid should not be exceeded). The dosages should theoretically be based on lean body weight. Dosing on a twice daily basis prevents large peaks and troughs in plasma concentration. The half-life of digoxin in the dog is reported to be 23-39 h. In the cat, a dose of 0.01 mg kg-1 every other day is recommended and a 30% reduction should be made if aspirin and frusemide are administered concurrently. Renal excretion of digoxin is an important route of elimination and reduced renal function will lead to toxicity occurring at these dose rates. Food will reduce the rate of absorption of digoxin from the gastrointestinal tract and the absorption characteristics will vary from one formulation to another. Use of digoxin can be facilitated by monitoring scrum levels of the drug which should fall between 1.0 and 2.5 ng ml-1. This therapeutic range should be achieved within three to five half-lives of starting therapy (that is within 3-5 days). Rapid digitalization by giving loading doses is rarely necessary and is associated with a higher incidence of toxicity.

Signs of digoxin toxicity (anorexia and vorniring) are due to the effects of the drug on the chemoreceptor trigger zone in the medulla. In addition, myocardial toxicity will result in cardiac arrhythmias, particularly of ventricular origin. Unfortunately, myocardial toxicity can occur without gastrointestinal signs, particularly in dogs with myocardial systolic failure. Hypokalaemia and hypomagnesaemia caused by diuretic therapy will enhance the toxicity of digoxin so blood plasma electrolyte concentrations should be monitored. Concurrent use of other drugs such as quinidine and verapamil will also increase the risk of toxicity, therefore a reduction in digoxin dosage should be made if these drugs are given in combination. In managing digoxin toxicity, electrolyte abnormalities should be corrected and ventricular arrhythmias treated with lignocaine.

Veterinary Medicine

Management Of Cardiac Arrhythmias

Abnormalities in the generation and / or the conduction of electrical impulses in the heart can give rise to an overall reduction in the heart rate (bradydysrhythmias) or a rapid heart rate (tachydysrhythinias). In both circumstances, cardiac function may be compromised. Slow rates (<50 bpm) lead to inadequate output despite a very large stroke volume and fast irregular rhythms lead to insufficient time for adequate filling of the heart during diastole, thus giving rise to low stroke volume. In addition, tachycardias which encroach on diastole will reduce the time for myocardial blood flow and lead to ischaemia of the heart muscle. In any situation where cardiac function is already compromised, the development of an arrhythmia will tend to lead to decompensation and result in clinical signs of heart failure. Severe arrhythmias may give rise to an acute decrease in cardiac output and poor perfusion of the brain leading to loss of consciousness (syncope). It is important to remember that the presence of a cardiac arrhythmia does not necessarily indicate a primary cardiac problem; it may be an indication of a number of systemic problems (for example electrolyte, neurological, gastrointestinal disorders and circulatory shock of non-cardiac origin).

In some circumstances, the underlying cause of the arrhythmia will be amenable to specific treatment or will be self-limiting and the arrhythmia will resolve without anti-arrhythmic drug treatment. In other cases, the effects of the arrhythmia may be life-threatening or the underlying cause cither cannot be diagnosed or is not amenable to treatment. Here, symptomatic anti-arrhythmic drug therapy is indicated. It is important to recognize those situations where cardiac arrhythmias may occur so that they can be detected early and the patient can be monitored to determine whether anti-arrhythmic therapy is necessary.

In the following discussion of the management of different cardiac arrhythmias, a brief overview of the possible underlying causes is given followed by practical decisions concerning therapy and the realistic goals of such therapy. The diagnostic electrocardiographic features of specific cardiac arrhythmias are described in site.



The sinus node can be driven by excessive stimulation of sympathetic tone to discharge at a rate which begins to compromise cardiac function leading to sinus tachycardia. Rapid heart rates may also result from abnormalities in automaticity and or conduction which lead to cardiac arrhythmias. Electrophysiological mechanisms involved in the pathogenesis of tachydysrhythmias include:

Ectopic foci, which reach threshold before the sinus nodal tissue causing premature beats or sustained tachycardia.

Afterdepolarizations, which occur in the repolarization phase of a normal beat (hence are described as triggered activity).

Re-entry which occurs when an electrical impulse circulates around a conduction pathway, exciting the rest of the heart each time it does. If the circulation of a re-entrant rhythm is continuous, a sustained ectopic rhythm will develop (for example atrial fibrillation). Intermittent circulation will lead to paroxysmal episodes of tachycardia.

A surface ECG does not distinguish which electrophysiological mechanism predominates in the arrhythmia but consideration of the cellular mechanisms responsible for arrhythmogenesis does enable an appreciation of the mechanism of action of antidysrhythmic drugs. Site shows a schematic diagram of the pathogenesis of tachydysrhythmias and the sites at which antidysrhythmic drugs act to suppress such arrhythmias. Hypoxic, damaged heart tissue has a less negative resting membrane potential and hence could reach threshold and fire more quickly than the sinoatrial node and so, potentially, could give rise to ectopic foci. Catecholamines will speed the rate at which the diastolic membrane potential drifts towards threshold and so can contribute to the generation of ectopic impulses. Triggered activity is thought to occur when cardiac muscle cells become overloaded with calcium in their cytoplasm. Hypoxia will reduce the efficiency with which calcium is extruded from the cytoplasm or pumped into intracellular stores. Drugs, such as digoxin, will lead to cellular overload with calcium, hence their arrhythmogenic potential. Conditions which favour re-entry include a long conduction pathway (stretched myocardium), slow conduction (a low safely margin for conduction leading to a unidirectional block as occurs in damaged, hypoxic tissue) and rapid repolarization (an effect of catecholamine stimulation).

Supraventricutar tachydysrhythmias

Ventricular arrhythmias

Veterinary Medicine


Symptomatic bradycardia results from problems of impulse generation in the sinus node and / or its conduction from the atria to the ventricles. Both of these processes are influenced by the autonomic nervous system with the parasympathetic system slowing and the sympathetic system accelerating impulse generation and conduction.

Non-cardiac causes of bradycardia

Sinus bradycardia is often a normal finding in athletic dogs (50 bpm or below) and is rarely associated with clinical signs. Even in dogs showing signs of vague illness, such as lethargy, which demonstrate mild sinus bradycardia, use of drugs which increase the heart rate (for example atropine) does not usually improve their behaviour. Profound symptomatic bradycardia may be caused by a number of factors which do not involve organic cardiac disease, some of which are shown in site. In many cases It is an alteration in the balance between parasympithetic and sympathetic tone to the heart which results in bradycardia so that therapy with antimuscarinic drugs (particularly where vagal tone is raised) or beta-adrenoceptor agonists is indicated to increase heart rate together with supportive therapy such as intravenous fluids and warmth. It is important to consider the underlying cause before using such symptomatic therapy as it may not always be indicated. For example, use of atropine to control bradycardia following the administration of an alpha2-adrenoceptor agonist may potentiate the transient hypertension which results after administration of such drugs to dogs and cats. Administration of beta-adrenoceptor agonists to increase the heart rate in a dog with bradycardia due to digoxin toxicity would increase the potential for ventricular tachycardia to develop. Thus, where possible, specific therapy should be administered based on the diagnosis of the underlying cause. These extrinsic factors should be considered before diagnosing the cause of symptomatic bradycardia as being due to organic disease of the sinoatrial node or of the conducting pathways in the heart.

Symptomatic bradycardia associated with organic cardiac disease

Sick sinus syndrome

This term is used to describe idiopathic disorders of the sinoatrial node, where the animals show signs of intermittent sinus arrest, sinoatrial block or sinus bradycardia. The subsidiary pacemakers fail to generate adequate escape rhythms. Some cases also show intermittent supraventricular tachyarrhythmias which may contribute to the clinical signs. This is a heterogeneous and imprecisely defined group of conditions rather than a single disease. Miniature schnauzers, pugs and dachshunds have been reported as presenting with this syndrome but it has also been seen in mixed breed dogs. In the management of this condition, it is important to manage the bradycardia first before treatment of the tachycardic episodes can be undertaken safely.

Persistent atrial standstill (silent atrium)

In persistent atrial standstill the sinus node fails to generate electrical impulses and the heart rate is governed by supraventricular, functional or ventricular escape beats. This condition is rare in dogs and cats and should be distinguished from the potentially reversible sinoventricular rhythm which accompanies severe and life-threatening hyperkalaemia.

Atrioventricular block

Failure or delay in the conduction of the sinoatrial impulse may be classified as first, second (Mobitz type I and II) or third degree atrioventricular block. In some cases, heart block can be intermittent and therefore more difficult to diagnose without the use of a continuous ambulatory ECG. First degree atrioventricular block and Mobitz type 1 seconddegree atrioventricular block are common in the dog and rarely signify intrinsic disease of the conducting system. They are easily abolished following exercise or atropine administration (0,02-0.04 mg kg-1 i.m. or i.v.). Atropine may cause an initial increase in the severity of the block (by a central action) but within 10-15 min sinus rhythm results. By contrast, in the cat even low-grade heart block is an abnormal finding and warrants further investigation.

Idiopathic persistent high-grade second-degree and complete (third degree) atrioventricular block occur in middle-aged or older dogs and are often associated with clinical signs. These may consist of weakness, exercise intolerance and syncope. Idiopathic third degree atrioventricular black has been reported in the dog in association with acquired myasthenia gravis. If obvious organic heart disease can be identified, the prognosis is much worse than for idiopathic cases where no obvious pathological process can be detected. Drug toxicity (calcium channel blockers, digoxin, beta-adrenoceptor antagonists) or electrolyte disturbances (hyperkalaemia) should be ruled out as possible causes of atrioventricular block.

Medical management of symptomatic bradycardia due to organic heart disease

Pacemaker implantation is the only long-term solution to animals exhibiting high-grade second-degree or complete atrioventricular block, persistent atrial standstill, and many cases of sick sinus syndrome. In an emergency, heart rate can be best increased by using beta-adrenoceptor agonists such as isoprenaline (10 ng kg-1 mm-1) or dopamine (2-10 μg kg-1 min-1), given by continuous intravenous infusion. An oral dose rare of isoprenaline has been described (5-10 mg three to four times daily) but there is less scope for the clinician to control the effects of the drug. Dopamine is the preferred choice since it lacks the profound peripheral vasodilatation in skeletal muscle which occurs following isoprenalinc administration. Although these drugs can be life-saving in severe cases before pacemaker implantation, their use can be associated with the occurrence of ventricular tachyarrhythmias. These should be controlled by stopping the infusion of the drug and not by the administration of drugs which suppress ventricular arrhythmias (for example lignocaine) since such drugs will suppress the escape rhythms which maintain some cardiac output in these animals.

Antimuscarinic drugs often fail to increase the heart rate in animals with heart block and atrial standstill since high vagal tone is not involved in the pathogenesis of these arrhythmias- Junctional escape rhythms may sometimes increase in rate when antimuscarinic drugs are used and some dogs with sick-sinus syndrome can be managed chronically with such drugs. Test doses of atropine will demonstrate those cases where such therapy may be worth trying. Oral preparations of antimuscarinic agents include propantheline bromide (7.5-15 mg three times daily for dogs). In dogs with both bradycardia and tachycardia, administration of antimuscarinic drugs may worsen the episodes of Tachycardia as these drugs increase conduction through the atrioventricular node. In these cases, the bradycardia should be managed by the use of a pacemaker and drugs which suppress the supraventricular tachycardia can then be safely employed. The use of pacemakers to treat symptomatic bradycardias has been extensively covered by others.

Veterinary Medicine

Supraventricutar tachydysrhythmias

Sinus tachycardia (heart rates greater than 160-180 bpm in the dog and 240 bpm in the cat respectively) can occur in response to pain> fright, fever, anaemia, circulatory shock and hyperthyroidism, all states where sympathetic tone to the heart increases and as a result, the rate of impulse generation and conduction is enhanced. Drugs such as levothyroxine and bronchodilators such as terbutaline, if given in excess, may produce sinus tachycardia as a side effect. Treatment of the underlying condition (or cessation of the offending drug) will be sufficient, in most cases, to reduce the heart rate and drug therapy is not usually necessary.

Supraventricular tachydysrhythmias develop, most commonly, in animals where there is stretch of the atria (particularly the left atrium), for example, in dogs with dilated cardiomyopathy or mitral valvular insufficiency, and in cats with hypertrophic cardiomyopathy. Some congenital defects such as mitral and tricuspid dysplasia, patent ductus arteriosus and ventricular septal defect, which lead to atrial stretch, are also associated with supraveniricular tachydysrhythmias. The larger the normal heart size of the animal, the more readily supraventricular arrhythmias (particularly atrial fibrillation) will be supported. Indeed, a recent survey has shown that in Irish wolfhounds the incidence of atrial fibrillation is about 10% in apparently healthy animals. Size, however, does not appear to be the only factor involved as the same survey found no cases of atrial fibrillation in normal Old English mastiffs.

Management of supraventricular tachydysrhythmias

Most commonly, paroxysmal or sustained atrial tachydysrhythmias (usually atrial fibrillation) are associated with animals showing signs of congestive heart failure. Management of these arrhythmias should be part of the treatment of the heart failure since an uncontrolled heart rate will lead to severe compromise of cardiac function. Digoxin is the drug of choice in the management of these cases (with the exception of re-entrant supraventricular tachycardia occurring in animals with ventricular pre-excuation syndrome, where it is contraindicated) since it is the only drug currently available which slows conduction through the AV node without reducing myocardial contractility. This is particularly important in animals with poor systolic function as is the case in dilated cardiomyopathy. In severe cases of congestive heart failure due to dilated cardiomyopathy, it may be desirable to give a more effective positive inotrope, such as dobutamine. Dobutamine, however, will tend to increase conduction through the atrioventricular node, thus accelerating the ventricular response rate in atrial fibrillation. Concurrent treatment with digoxin will tend to reduce the ventricular response rate. If possiblel slow digitalization is recommended (see earlier for dose rates). High loading doses are dangerous, particularly in dogs which are hypoxic and have poor myocardial contractility.

Digoxin will not convert atrial arrhythmias into sinus rhythm but reduces the significance of the arrhythmia by slowing the ventricular response. The ideal ventricular rate which should be aimed for in the management of atrial arrhythmias has not been determined for the dog or cat. Most cardiologists would suggest that rates in excess of 160 bpm in the dog under examination conditions are too high. Some suggest training the owners to record the heart rate at home using a stethoscope and suggest a target: rate of between 70 and 110 bpm in the dog and 80-140 bpm in the cat. Such heart rates can rarely be achieved by the use of digoxin alone. Measurement of serum digoxin levels should be made after 5 days on maintenance therapy to ensure that the therapeutic serum concentration of digoxin has been achieved but not exceeded. Additional drug therapy may then be instituted in an attempt to reduce the heart rate further

The second drug recommended for use in atrial arrhythmias is diltiazem (0.5 mg kg-1 three times daily for dogs, twice daily for cats). Diltiazem is a calcium channel blocker which has effects on both cardiac and vascular smooth muscle. Conduction of electrical impulses through the atrioventricular node relies on slow calcium channels and diltiazem slows conduction through the atrioventricular node. It has the potential to reduce cardiac muscle contractility, which partly depends on calcium entry during the cardiac action potential. Diltiazem is thought to have less of a negative inotropic effect when compared with verapamil, possibly because it also reduces afterload whereas verapamil is less effective in this respect. Both verapamil and diltiazem reduce the excretion of digoxin which may necessitate a reduction in the dose of digoxin if combined with a calcium channel blocker. Calcium channel blockers are the drugs of choice in the management of re-entrant supraventricular tachycardia in animals with ventricular pre-excitation syndrome. Conversion of atrial arrhythmias into a normal sinus rhythm has been reported following the use of calcium channel blockers (Johnson, 1984)+ The conversion is short-lived in animals with underlying cardiac disease unless therapy is maintained. The arterial vasodilator properties of diltiazem will also reduce afterload and enhance coronary blood flow during diastole.

Beta-adrenoceptor antagonists can also be used to reduce the ventricular response rate in cases of supraventricular tachydysrhythmia. Propranolol is a non-selective beta-adrenoceptor antagonist which can be used for this purpose at an oral dose rate of 0.5-1 mg kg-1 twice or three times daily. The negative inotropic effect of propranolol will be particularly marked in animals relying on sympathetic drive to compensate for poor myocardial contractility. Beta-blockers, therefore, should be used with caution in any animal with signs of congestive heart failure, particularly when poor systolic function is likely to be the underlying cause. Cardioselective beta-blockers have been produced, with the main advantage that they show less tendency, compared with propranolol, to precipitate asthmatic attacks by blocking the protective bronchodilator effect of circulating adrenaline. Dose rates are available for drugs such as atenolol and metoprolol but we currently lack experience with the use of such drugs in veterinary medicine.

It should be remembered that digoxin, calcium channel blockers and beta-blockers all decrease conduction through the atrioventricular node via different mechanisms and so will have a synergistic effect when administered together. When introducing a second drug, close monitoring of the patient is necessary to ensure that excessive reduction in the heart rate does not occur Recently, adenosine has been used in human medicine to convert unstable supraventricular tachycardia into sinus rhythm and the development of drugs with favourable pharmacokinctics which are selective for cardiac adenosine receptors may, in the future, add to the therapeutic alternatives available for the management of supraventricular tachydysrhythmias.

With atrial tachydvsrhythmias of sudden onset following surgery or trauma, where there is no sign of cardiomegaly or congestive heart failure, it may be reasonable to attempt to convert the rhythm into normal sinus rhythm. This can be attempted by the use of quinidine or diltiazem. Quinidine has antimuscarinic properties and so may increase the ventricular rate initially before converting the rhythm back into sinus rhythm. For this reason, it is recommended to digitalize the animal before attempting conversion with quinidine. When administering quinidine with digoxin, it should be remembered that quinidine displaces digoxin from skeletal muscle binding sites so raising the serum concentration of digoxin. A 50% reduction in the digoxin dose is recommended under these circumstances.

Animals (usually large breed dogs) with atrial fibrillation where the ventricular response rate is relatively slow (<150 bpm) and where there is no evidence of heart failure are likely to develop problems eventually. When they are not showing clinical signs it is reasonable to follow them and give no therapy, particularly as the optimum heart rate for a dog with atrial fibrillation has not been established.


Canine Heartworm Disease: Complications And Specific Syndromes

Asymptomatic Heartworm Infection

Most dogs with heartworm infection are asymptomatic, even though many of these have heartworm disease (radiographic and pathologic lesions). Treatment is as described previously, using melarsomine in the split-dose regimen, along with a macrolide preventative.

Asymptomatic dogs may, however, become symptomatic af’er adulticidal therapy due to postadulticidal thromboembolization and lung injury (as “described elsewhere). The risk of postadulticidal thromboembolization can be imperfectly predicted by semiquantitation of the worm burden, using certain antigen tests, and by the severity of radiographic lesions. Clearly a dog with severe radiographic lesions will not tolerate thromboembolic complications well, but not all dogs with radiographic signs have heavy worm burdens. For example, a dog with moderate to severe radiographic lesions and high antigenemia may not be at high risk for postadulticidal PTE, because it is quite possible that the worms have died, explaining both the antigenemia (release from dead worms) and radio-graphic abnormalities (chronic HWD).This conclusion might also be valid in the dogs with severe radiographic lesions and negative or low antigenemia (assumes most or all worms have died, and antigen has been cleared). Alternatively, antigenic evidence of a heavy worm burden in a dog with minimal radiographic signs might still portend a severe reaction after melarsomine, because the findings suggest large worm numbers but without natural worm attrition (i.e., a relatively young infection with minimal disease). Of course, low worm burden and minimal radiographic lesions would suggest the least risk of an adverse reaction to adulticide.

It bears emphasis that with each scenario, guesswork is involved and precautions should be taken. When the risk is greatest, aspirin (5 to 7 mg/kg daily — begun 3 weeks prior to and continued until 3 weeks after adulticide) or even heparin may be used, and cage confinement is most important. The owners should be educated as to the risk, the suggestive signs, and the importance of prompt veterinary assistance in case of an adverse reaction.


The majority of dogs suffering from chronic HWI have glomerulonephritis, which can be severe. Therefore when a dog demonstrates glomerular disease, heartworm infection should be considered as a differential diagnosis. Although it is generally felt that the glomerular lesions produced by heartworm infection are unlikely to produce renal failure, a therapeutic dilemma results when one is found in a dog with proteinuria, azotemia, and HWI. Logic suggests that adulticidal therapy is indicated because heartworm infection contributes to glomerular disease, but it likewise carries risks. The approach embraced by this author is to hospitalize the patient and to administer intravenous fluids (lactated Ringer’s solution at 2 to 3 mL/kg/hr) for 48 hours (beginning 12 hours prior to the first melarsomine dose). The patient is then released, and a recheck appointment for blood urea nitrogen (BUN) and creatinine determination after 48 hours is advised. The second and third injections are tentatively scheduled for 1 to 3 months, with the treatment decision based on renal function and the overall response to initial adulticidal therapy.

Allergic Pneumonitis

Allergic pneumonitis, which is reported to affect 14% of dogs with HWD, is a relatively early development in the disease course. In fact, the pathogenesis probably involves immunologic reaction to dying microfilariae in the pulmonary capillaries. Clinical signs include cough and sometimes dyspnea and other typical signs of HWD, such as weight loss and exercise intolerance. Specific physical examination findings may be absent or may include dyspnea and audible crackles in more severe cases. Radiographic findings include those typical of heartworm disease but with an infiltrate, usually interstitial, but occasionally with an alveolar component, often worse in the caudal lung lobes. Eosinophils and basophils may be found in excess in peripheral blood and in airway samples. Corticosteroid therapy (prednisone or prednisolone at 1 to 2 mg/kg per day) results in rapid attenuation of clinical signs, with radiographic clearing in less than a week. The dose can then be stopped in 3 to 5 days if clinical signs subside. Although microfilaricidal therapy is typically not indicated because infections are often occult, macrolide prophylaxis is indicated to avoid further infection. Adulticidal therapy can be used after clinical improvement.

Eosinophilic Granulomatosis

A more serious, but rare, manifestation, pulmonary eosinophilic granulomatosis, responds less favorably. This syndrome is characterized by a more organized, nodular inflammatory process, associated with bronchial lymphadenopathy and, occasionally, pleural effusion. With pulmonary granulomatosis, cough, wheezes, and pulmonary crackles are often audible; when very severe, lung sounds may be muffled and associated with dyspnea and cyanosis. Treatment with prednisone at twice the dose for allergic pneumonitis is reported to induce partial or complete remission in 1 to 2 weeks. The prognosis remains guarded because recurrence within several weeks is common. Prednisone may be combined with cyclophosphamide or azathioprine in an effort to heighten the immunosuppressive effect. The latter combination appears to be the most effective Adulticide therapy should be delayed until remission is attained. As the prognosis for medical success is guarded; surgical excision of lobar lesions has been advocated.

Pulmonary Embolization

Spontaneous thrombosis or postadulticidal thromboembolization associated with dead and dying worms — the most important heartworm complication — may precipitate or worsen clinical signs, producing or aggravating PHT, right heart failure or, in rare instances, hemoptysis and pulmonary infarction. Acute fatalities may result from fulminant respiratory failure, exsanguination, DIC, or may be unexplained and sudden (arrhythmia or massive pulmonary embolism). The most common presentation, however, is a sudden onset of lethargy, anorexia, and cough 7 to 10 days after adulticidal therapy — often after failure to restrict exercise. Dyspnea, fever, mucous membrane pallor, and adventitial lung sounds (crackles) may be noted on physical examination. Thoracic radiographs reveal significant pulmonary infiltrates, most severe in the caudal lung lobes.

The degree of worsening, as compared with pretreatment radiographs, is typically dramatic. The infiltrate, typically alveolar, is most severe in the caudal lobes, and occasionally areas of consolidation are noted. Laboratory abnormalities vary with the severity of signs but may include leukocytosis, left shift, monocytosis, eosinophilia, and thrombocytopenia. The degree thrombocytopenia may provide prognostic information.

Medical management of thromboembolic lung disease is largely empiric and somewhat controversial. It is generally agreed that strict cage confinement, oxygen administration via oxygen cage or nasal insufflation (50 to 100 mL/kg), and prednisone (1 mg/kg/day for 3 to 7 days) are indicated in the most severe cases. KMW Some advocate careful fluid therapy (see recommendations for CS), measuring CVP to avoid precipitation of heart failure, to maximize tissue perfusion and combat dehydration. The use of heparin (75 IU/kg subcutaneously three times a day until platelet count has normalized [5 to 7 days]) and aspirin (5 to 7 mg/kg/day) has been advocated y some but remains controversial.

Other therapeutic strategies might include cough suppressants, antibiotics (if fever is unresponsive), and, although speculative at this time, vasodilators (amlodipine, hydralazine, diltiazem). If vasodilatory therapy is used, one must monitor blood pressure because hypotension is a potential side effect. Clinical improvement may be rapid and release from the hospital considered after several days’ treatment. For less severely affected dogs, careful confinement and prednisone at home are often adequate.

Congestive Heart Failure

Right heart failure results from increased right ventricular afterload (secondary to chronic pulmonary arterial disease and thromboemboli with resultant PHT). When severe and chronic, pulmonary hypertension may be complicated by secondary tricuspid regur-gitation and right heart failure. Congestive signs (ascites) are worsened in the face of hypoproteinemia. Calvert suggests that up to 50% of dogs with severe pulmonary vascular complication to heartworm disease will develop heart failure. Clinical signs variably include weight loss, exercise intolerance, ashen mucous membranes with prolonged capillary refill time, ascites, dyspnea, jugular venous distension and pulsation, arrhythmias with pulse deficits, and adventitial lung sounds (crackles and possibly wheezes). Dyspnea may be due to pulmonary infiltrates (PIE or PTE, but not cardiogenic pulmonary edema), abdominal distension, or pleural effusion.

Treatment aims include reduction of signs of congestion, reducing PHT, and increasing cardiac output. This involves dietary, pharmacologic, and procedural interventions. Moderate salt restriction is logical and probably useful in diminishing diuretic needs. This author chooses a diet designed for senior patients or early heart disease, because salt restriction should only be moderate. Diuretics may be useful in preventing recurrence of ascites but are typically not able to mobilize large fluid accumulations effectively. This then requires periodic abdominal or thoracic paracentesis (or both) when discomfort is apparent. Furosemide is typically used at 1 to 4 mg/kg daily, depending on severity and patient response Additional diuretics, which provide a supplemental effect by using differing parts of the nephron, include spironolactone (1 to 2 mg/kg orally twice a day) and chlorothiazide (2 mg/kg orally daily to every other day). The ACE-inhibitors (eg., enalapril, benazepril, lisino-pril, ramipril), by their effect on the renin-angiotensin-aldosterone system, may be of use as mixed vasodilators, in blunting pathologic cardiac remodeling, and in reducing fluid retention, particularly cases of refractory ascites. Adulticide therapy is delayed until clinical improvement is noted. No evidence indicates that digoxin improves survival in HWD. Because of the risk of toxicity and pulmonary vasoconstriction associated with its use, it is not routinely used by is author in the management of HWD-induced heart failure However, digoxin may be beneficial in the presence of supraventricular tachycardia or refractory heart failure Aspirin, theoretically useful because of its ability to ameliorate some pulmonary vascular lesions and vasoconstriction, may be used 5 mg/kg/day orally.

The arterial vasodilator, hydralazine, has been shown by Lombard to improve cardiac output in a small number of dogs with heartworm disease and heart failure. It has also been demonstrated to reduce pulmonary artery pressure and vascular resistance right ventricular work, and aortic pressure without changing cardiac output or heart rate in dogs with experimental heartworm disease (but without heart failure). Clinical experience has shown perceived improvement with the vasodilators diltiazem and amlodipine as well. Research and clinical experience suggest that hydralazine, amlodipine, and diltiazem might have a role in this setting, but further studies are necessary to define their role, if any. In heart failure the author uses hydralazine at 0.5 to 2 mg/kg orally twice a day, diltiazem at 0.5 to 1.5 mg/kg orally three times a day, or amlodipine at 0.1 to 0.25 mg/kg/day orally. The risk of hypotension with these therapies must be realized and blood pressure monitored.

Often heart failure follows adulticidal therapy, but if it is present prior to adulticidal therapy, the difficult question arises as when (or whether) to administer melarsomine. If clinical response to heart failure management is good, adulticidal therapy may be offered in 4 to 12 weeks, as conditions allow. Melarsomine is generally avoided if heart failure is refractory. Antiarrhythmic therapy is seldom necessary, although slowing the ventricular response to atrial fibrillation with digoxin, Diltiazem, or both () may be necessary in some cases.

Caval Syndrome

Heartworm CS is a relatively uncommon but severe variant or complication of HWD. Most studies have shown a marked sex predilection, with 75% to 90% of CS dogs being male. It is characterized by heavy worm burden (usually >60, with the majority of the worms residing in the right atrium and venae cavae) and a poor prognosis.

Studies performed in the author’s laboratory indicate that retrograde migration of adult heartworms to the cavae and right atrium, from 5 to 17 months after infection, produces partial inflow obstruction to the right heart and, by interfering with the valve apparatus, tricuspid insufficiency (with resultant systolic murmur, jugular pulse, and CVP increase). Affected dogs also exhibit pre-existent heartworm-induced PHT, which markedly increases the adverse hemodynamic effects of tricuspid regurgitation. These combined effects substantially reduce left ventricular preload and hence cardiac output. Cardiac arrhythmias may further compromise cardiac function.

This constellation of events precipitates a sudden onset of clinical signs, including hemolytic anemia caused by trauma to red blood cells (RBCs) as they pass through a sieve of heart-worms occupying the right atrium and venae cavae, as well as through fibrin strands in capillaries if disseminated intravascular coagulation has developed. Intravascular hemolysis, metabolic acidosis, and diminished hepatic function with impaired removal of circulating pro-coagulants contribute to the development of DIC. The effect of this traumatic insult to the erythron is magnified by increased RBC fragility, due to alterations in the RBC membrane in dogs with HWD. Hemoglobinemia, hemoglobinuria, and hepatic and renal dysfunction also are observed in many dogs. The cause of hepatorenal dysfunction is not clear, but it probably results from the combined effects of passive congestion, diminished perfusion, and the deleterious effects of the products of hemolysis. Without treatment, death frequently ensues within 24 to 72 hours due to cardiogenic shock, complicated by anemia, metabolic acidosis, and DIC.

A sudden onset of anorexia, depression, weakness, and occasionally coughing are accompanied in most dogs by dyspnea and hemoglobinuria. Hemoglobinuria has been considered pathognomonic for this syndrome. Physical examination reveals mucous membrane pallor, prolonged capillary refill time, weak pulses, jugular distension and pulsation, hepatosplenomegaly, and dyspnea. Thoracic auscultation may disclose adventitial lung sounds; a systolic heart murmur of tricuspid insufficiency (87% of cases); loud, split S2 (67%); and cardiac gallop (20%). Other reported findings include ascites (29%), jaundice (19%), and hemoptysis (6%). Body temperature varies from subnormal to mildly elevated.

Hemoglobinemia and microfilaremia are present in 85% of dogs suffering from CS. Moderate (mean PCV, 28%) regenerative anemia characterized by the presence of reticulocytes, nucleated RBC, and increased mean corpuscular volume (MCV) is seen in the majority of cases. This normochromic, macrocytic anemia has been associated with the presence of target cells, schistocytes, spur cells, and spherocytes. Leukocytosis (mean white blood cell (WBC] count, approximately 20,000 cells/cm) with neutrophilia, eosinophilia, and left shift has been described. Dogs affected with disseminated intravascular coagulation are characterized by the presence of thrombocytopenia and hypofibrinoginemia, as well as prolonged one stage prothrombin time (PT), partial thromboplastin time (PTT), activated coagulation time (ACT), and high fibrin degradation product concentrations. Serum chemistry analysis reveals increases in liver enzymes, bilirubin, and indices of renal function. Urine analysis reveals high bilirubin and protein concentrations in 50% of cases and more frequently, hemoglobinuria.

CVP is high in 80% to 90% of cases (mean, 11.4 cm H20). Electrocardiographic abnormalities include sinus tachycardia in 33% of cases and atrial and ventricular premature complexes in 28% and 6%, respectively. The mean electrical axis tends to rotate rightward (mean, +129 degrees), with an S1,2,3 pattern evident in 38% of cases. The S wave depth in CV6LU (V<) is the most reliable indicator of right ventricular enlargement (>0.8 mv) in 56% of cases. Thoracic radiography reveals signs of severe heartworm disease with cardiomegaly, main pulmonary arterial enlargement, increased pulmonary vascularity, and pulmonary arterial tortuousity recognized in descending order of frequency (). Massive worm inhabitation of the right atrium with movement into the right ventricle during diastole is evident echocardiographically. This finding on M-mode and two-dimensional echocardiograms is nearly pathognomonic for CS in the appropriate clinical setting. The right ventricular lumen is enlarged and the left diminished in size, suggesting pulmonary hypertension accompanied by reduced left ventricular loading. Paradoxical septal motion, caused by high right ventricular pressure, is commonly observed. No echocardiographic evidence of left ventricular dysfunction exists. Cardiac catheterization documents pulmonary, right atrial, and right ventricular hypertension and reduced cardiac output.

Prognosis is poor unless the cause of the crisis — the right atrial and caval heartworms — is removed. Even with this treatment, mortality can approximate 40%.

Fluid therapy is needed to improve cardiac output and tissue perfusion, to prevent or help to reverse DIC, to prevent hemoglobin nephropathy, and to aid in the correction of metabolic acidosis. Overexuberant fluid therapy, however, may worsen or precipitate signs of congestive heart failure. In the author’s clinic, a left jugular catheter is placed and intravenous fluid therapy instituted with 5% dextrose in water or one-half strength saline and 2.5% dextrose. The catheter should not enter the anterior vena cava because it will interfere with worm embolectomy. A cephalic catheter may be substituted for the somewhat inconvenient jugular catheter, but this does not allow monitoring of CVP. The intravenous infusion rate for fluids is dependent on the condition of the animal. A useful guideline is to infuse as rapidly as possible (up to 1 cardiovascular volume during the first hour) without raising the CVP or without raising it above 10 cm H20 if it was normal or near normal at the outset. Initial therapy should be aggressive (10 to 20 mL/kg/hr for the first hour) if shock is accompanied by a normal CVP (<5 cm HzO), and it should be curtailed to approximately 1 to 2 mL/kg/hr if CVP is 10 to 20 cm HzO. Whole blood transfusion is not indicated in most cases because anemia usually is not severe, and transfused coagulation factors may worsen DIG Sodium bicarbonate is not indicated unless metabolic acidosis is severe (pH, 7.15 to 7.20). Broad-spectrum antibiotics and aspirin (5 mg/kg daily) should be administered. Treatment for disseminated intravascular coagulation is described elsewhere in this text.

The technique for surgical removal of caval and atria] heartworms was developed by Jackson and colleagues. This procedure should be undertaken as early in the course of therapy as is practical. Often, sedation is unnecessary, and the procedure can be accomplished with only local anesthesia. The dog is restrained in left lateral recumbency after surgical clipping and preparation. The jugular vein is isolated distally. A ligature is placed loosely around the cranial aspect of the vein until it is incised, after which the ligature is tied. Alligator forceps (20 to 40 cm, preferably of small diameter) are guided gently down the vein while being held loosely between the thumb and forefinger. The jugular vein can be temporarily occluded with umbilical tape. If difficulty is encountered in passage of the forceps, gentle manipulation of the dog by assistants to further extend the neck will assist in passage of the forceps past the thoracic inlet; medial direction of the forceps may be necessary at the base of the heart. Once the forceps have been placed, the jaws are opened, the forceps are advanced slightly, the jaws are closed, and the worms are removed. One to four worms are usually removed with each pass. This process is repeated until five to six successive attempts are unsuccessful. An effort should be made to remove 35 to 50 worms. Care should be taken not to fracture heartworm during extraction. After worm removal, the jugular vein is ligated distally, and subcutaneous and skin sutures are placed routinely. Other catheters, such as urethral stone basket catheters, horsehair brushes, snares and flexible alligator forceps have also been used. Fluoroscopic guidance, when available, is useful in this procedure.

Successful worm retrieval is associated with a reduction in the intensity of the cardiac murmur and jugular pulsations, rapid clearing of hemoglobinemia and hemoglobinuria, and normalization of serum enzymatic aberrations. Immediate and latent improvement in cardiac function occurs over the next 24 hours. It is important to realize that removal of worms does nothing to reduce right ventricular afterload (PHT), and hence fluid therapy must be monitored carefully before and after surgery to avoid precipitation or worsening of right heart failure. Cage rest should be enforced for a period of time suitable for individual care.

Worm embolectomy through a jugular venotomy is frequently successful in stabilizing the animal, allowing adulticide therapy to be instituted to destroy remaining heartworms in a minimum of 1 month. Careful scrutiny of BUN and serum liver enzyme concentrations should precede the latter treatment. Aspirin therapy is continued for 3 to 4 weeks after adulticide therapy. Substantial improvement in anemia should not be expected for 2 to 4 weeks after worm embolectomy. Macrolide preventative therapy, as described previously, is administered at the time of release from the hospital.

Aberrant Migration

Although heartworms in the dog typically inhabit the pulmonary arteries of the caudal lung lobes, they may find their way to the right ventricle, and rarely (see Caval Syndrome) the right atria and venae cavae. Much less frequently, immature L5 may aberrantly migrate to other sites, including the brain, spinal cord, epidural space, anterior chamber of the eye, the vitreous, the subcutis, and the peritoneal cavity. In addition, the worms may inhabit the systemic circulation, producing systemic thromboembolic disease. Treatment of aberrantly migrating heartworms requires either nothing (e.g., peritoneal cavity), surgical excision of the offending parasite, adulticidal therapy, or symptomatic treatment (e.g., seizure control with brain migration). The method for surgical removal from internal iliac and femoral arteries has been described.


Dilated Cardiomyopathy: Chronic Therapy

Diuretic Therapy

Diuretics are the only drugs that can routinely control the clinical signs referable to congestion and edema due to heart failure. Consequently, it is mandatory for cats with congestive heart failure to be on a diuretic, usually furosemide. The chronic orally administered dose for furosemide in cats is wide and ranges from 0.5 mg/lb a day to 2 mg/lb every 8 hours. The most common doses are 6.25 to 12.5 mg per cat every 8 to 12 hours, orally. In general, cats need a lower dose of furosemide when compared with dogs, although the upper end of the dose range can be similar. The goal of diuretic therapy is to keep pulmonary edema and pleural effusion controlled. This should be done with the lowest possible furosemide dose, although in the author’s experience, underdosing appears to be a more frequent problem than does overdosing. Every owner should be instructed to count his or her cat’s respiratory rate at home when the cat is sleeping or resting quiedy in a cool environment and to keep a written log. The normal respiratory rate for a cat is in the 20 to 40 breaths per minute range. If the rate is greater than 40 breaths per minute or the owner notes that the character of breathing is more labored, these are signals that an increased dose of furosemide, pleurocentesis, or both are needed. Changes in furosemide dose should be done in consultation with a veterinarian during the initial stages of management. Some owners will require continued contact with a veterinarian to manage dose changes, whereas others will reach a point where they feel comfortable doing this on their own. Cats with severe disease that require a maximum dose of furosemide are often mildly to moderately dehydrated and mildly to moderately azotemic. As long as they continue to eat, drink, and appear comfortable, the dose of furosemide should not be decreased. If the dehydration or azotemia becomes severe enough to cause anorexia, the furosemide administration must be discontinued as long as the cat is not taking in fluid. Owners must be warned that continued use of high-dose furosemide administration in a cat that is not drinking or eating can result in severe, life-threatening dehydration. Judicious use of parenteral fluid administration may be required. These, of course, are poor prognostic signs. Cats that are refractory to the maximum dose of furosemide may need to have another diuretic administered along with the same maximum dose of furosemide. Choices include a thiazide diuretic and possibly spironolactone. () Parenteral administration of furosemide may also be beneficial because the oral bioavailability of the drug is only around 50%.


Repeated pleurocentesis is often required in cats with pleural effusion. Pleurocentesis may need to be done as infrequently as once a month or as frequendy as every 4 or 5 days. As much fluid as possible should be removed at each visit. Ultrasound guidance often helps identify regions where fluid has pocketed. Chylothorax secondary to heart failure can result in chylofibrosis, making it very difficult to remove as much fluid as one would like. Risks of repeated pleurocentesis include infection, pneumothorax, and bleeding, but all are rare.

Angiotensin-Converting Enzyme Inhibitors

Any cat with idiopathic dilated cardiomyopathy should be on an angiotensin-converting enzyme (ACE) inhibitor for long-term management unless they have an adverse reaction to the drug. Enalapril is most commonly used at a dose of 1.25 to 2.5 mg per cat orally every 24 hours. angiotensin-converting enzyme inhibitors can almost never be used on their own to control signs of heart failure and are not effective for controlling heart failure in the acute care setting. Rather they must be administered in concert with a diuretic and help in the long-term control of the disease. Generally, angiotensin-converting enzyme inhibitor therapy should be started when the cat is reasonably stable and not dehydrated.


Digoxin, in theory, may be administered to cats with dilated cardiomyopathy. However, in the initial trial that identified taurine deficiency as a cause of feline dilated cardiomyopathy, digoxin was not administered and most of those cats survived; therefore clearly in cats with dilated cardiomyopathy due to taurine deficiency, no clear mandate exists to administer digoxin.

Dietary Modifications

Any cat with dilated cardiomyopathy should be supplemented with 250 mg taurine orally every 12 hours until the results of the plasma and whole blood taurine concentration analysis are evaluated. Taurine is inexpensive and can be purchased from health food stores or chemical supply houses. Cats that are taurine deficient should be continued on taurine supplementation, whereas those that are not may be taken off or left on at the discretion of the owner. Sodium-restricted diets may be useful, particularly in cats that are refractory to drug therapy. However, it is more important to keep the cat eating than it is to force sodium restriction.


Arrhythmocenic Right Ventricular Cardiomyopathy

ARVC is a recendy reported and rare form of feline cardiomyopathy. It has been identified in humans, dogs (boxer dogs), and cats. It is characterized by fibrofatty or fatty infiltration of primarily the right ventricular free wall. The right ventricular wall is commonly thinned in humans and cats with the disease. Ventricular tachyarrhythmias are common in all three species, and sudden death is a common feature of the disease in humans and boxer dogs. The disease is also commonly known as arrhythmogenic right ventricular dysplasia (ARVD).

Cause of Arrhythmocenic Right Ventricular Cardiomyopathy

The cause of arrhythmogenic right ventricular cardiomyopathy is unknown in cats. In humans at least six forms of the disease (ARVD 1 to 6) are inherited as an auto-somal dominant trait, and one (Naxos syndrome) is inherited as an autosomal recessive trait.Iu The cause of ARVD 2 has been recently identified as several mutations in the gene that encodes for the calcium release channel (also known as the ryanodine receptor) on the myocardial sarcoplasmic reticulum. Ryanodine receptor dysfunction has been identified in boxer dogs with ARVC.

Pathophysiology of Arrhythmocenic Right Ventricular Cardiomyopathy

In cats, arrhythmogenic right ventricular cardiomyopathy most commonly (8 of 12 cats in the one study reported to date) produces right heart failure, presumably through the destruction of right ventricular myocardium resulting in right ventricular systolic and, possibly, diastolic dysfunction along with secondary tricuspid regurgitation. The changes in the right ventricular free wall also commonly produce ventricular tachyarrhythmias (9 of 12 cats) and supraven-tricular tachyarrhythmias (5 of 12 cats). Tumor necrosis factor (TNF) is commonly increased in cats with right heart failure, which may contribute to the systemic effects of the disease.

Pathology of Arrhythmocenic Right Ventricular Cardiomyopathy

The right ventricular and atrial chambers are markedly enlarged in cats that die of the disease.IH Thinning of the right ventricular free wall is a consistent feature of the disease and may be focal or diffuse. Aneurysms of the wall may occur, especially at the apex of the right ventricle (RV). The wall is often so thin that light can be seen through it. Histopathologically either fibre-fatty or fatty replacement of myocardium exists. Inflammatory cells are commonly present, especially in regions of fibrofatty replacement. Although most prominent in the right ventricular free wall, these changes are also commonly present in the left ventricular and occasionally identified in the left atrium. Apoptosis is common.

Clinical Manifestations

Evidence of right heart failure, including ascites, pleural and pericardia! effusions, and jugular vein distension, is common. The pleural effusion may be severe enough to cause tachypnea and dyspnea. A heart murmur secondary to tricuspid regurgi-tation is common. Arrhythmias are also commonly heard on auscultation, and ECG evidence of a ventricular arrhythmia may be one clue that one is dealing with arrhythmogenic right ventricular cardiomyopathy and not tricuspid valve dysplasia. Supraventricular tachyarrhythmias, including atrial fibrillation, may also occur. In the severe stage, echocardiography reveals marked enlargement of the right ventricular and right atrial chambers. The right ventricular chamber enlargement may be segmental. Tricuspid regurgitation is usually present on color flow Doppler. Careful echocardiographic interrogation may reveal localized regions of right ventricular wall thinning or regions of aneurysmal dilation. The right ventricular trabeculae may appear abnormal, especially at the apex. The disease may not be confined to the right heart, which means the left atrial and ventricular chambers may also be enlarged. Syncope due to ventricular tachycardia may be present.

Differential Diagnosis

Cats with severe arrhythmogenic right ventricular cardiomyopathy are commonly misdiagnosed as having tricuspid valve dysplasia because tricuspid regurgitation is a common sequel to the disease. Cats from 1 to 20 years of age have been diagnosed with the disease.

Therapy of Arrhythmocenic Right Ventricular Cardiomyopathy

Right heart failure is treated with furosemide and an angiotensin-converting enzyme inhibitor. Digoxin combined with either diltiazem or atenolol may be used to control supraventricular tachycardia or the ventricular rate in cats with atrial fibrillation. Malignant ventricular tachycardia or ventricular tachycardia that causes clinical signs (eg., syncope) can be managed acutely with lidocaine (5 to 20 µg/lb/min) and chronically with sotalol (1 to 2 mg/lb every 12 hours orally).


Management of Chronic Mitral Valve Insufficiency

Ideally, therapy of chronic mitral valve insufficiency would halt the progression of the valvular degeneration. Improvement of valvular function by surgical repair or valve replacement would likewise stop further deterioration. However, no therapy is currently known to inhibit or prevent the valvular degeneration, and surgery is usually not technically, economically, or ethically possible in canine and feline patients. The management of chronic mitral valve insufficiency is therefore concerned with improving quality of life, by ameliorating the clinical signs and improving survival. This usually means that therapy is tailored for the individual patient, owner, and practitioner and often involves concurrent treatment with two or more drugs once signs of heart failure are evident. Management of chronic mitral valve insufficiency will be discussed in five groups of patients: those without overt signs of heart failure (asymptomatic), those with left mainstem bronchial compression, those with syncope, those with mild to moderate heart failure, those with recurrent heart failure, and those with severe and fulminant heart failure. Possible complications are discussed separately. It is unusual to treat cases of isolated chronic mitral valve insufficiency in cats and details of drug dosages for cats are therefore not included in this section.

Asymptomatic Disease

The stage when a patient starts to show clinical signs of chronic mitral valve insufficiency (CMVI), that is, have developed decompensated heart failure, is the end of a process started much earlier with the onset of valve leakage. The valvular leakage was compensated through a variety of mechanisms but as the leakage increases the valves eventually became incapable of preventing pulmonary capillary pressures from exceeding the threshold for pulmonary edema, and of maintaining forward cardiac output. It is likely that minor signs of reduced activity and mobility are present even before overt signs of heart failure develop. However, it is very difficult to objectively evaluate the presence of slight to moderately reduced exercise capacity in most dogs with chronic mitral valve insufficiency (CMVI), as they are often old small companion dogs, which if obese, have little, if any, demand on their exercise capacity. Furthermore, other concurrent diseases in the locomotor system or elsewhere are common and restrict exercise. Thus vague clinical signs such as slightly reduced exercise capacity in a typical dog with progressed chronic mitral valve insufficiency may or may not be attributable to chronic mitral valve insufficiency (CMVI).

This dilemma leads to the questions of when to start therapy, and if therapy before the onset of decompensated heart failure is beneficial, ineffective, or harmful. ACE-inhibitors are frequently prescribed to dogs with chronic mitral valve insufficiency before the onset on heart failure. At present, however, there is no evidence that administration of any medication to a patient with asymptomatic chronic mitral valve insufficiency has a preventive effect on development and progression of clinical signs of heart failure or improves survival. Two large placebo-controlled multicenter trials, the SVEP and the VetProof trials, have been conducted to study the effect of monotherapy of the ACE-inhibitor enalapril on the progression of clinical signs in asymptomatic chronic mitral valve insufficiency in dogs. Both failed to show a significant difference between the placebo and the treatment groups in time from onset of therapy to confirmed congestive heart failure.H’ The two trials differ in the following features: the SVEP trial included

only dogs of one breed (Cavalier King Charles spaniels) whereas the VetProof trial included a variety of breeds. The dogs in the VetProof trial were more frequently progressed cases of chronic mitral valve insufficiency than the dogs in the SVEP trial, and the SVEP trial comprised more dogs than the VetProof trial (229 versus 139 dogs). Suggested reasons for the non-significant findings in these trials include lack of activation of circulating RAAS activity in asymptomatic animals, low concentration of angiotensin II receptors in the canine mitral valve, or lack of effect of ACE-inhibitors on myocardial remodeling and progressive ventricular dilatation in mitral regurgitation (MR).

Owners of dogs with progressed asymptomatic chronic mitral valve insufficiency should be instructed about signs of developing heart failure and, in case of breeding, about the fact that the disease is significantly influenced by genetic factors. The disease may be monitored at regular intervals of 3 to 12 months if significant cardiomegaly is present. Milder cases do not warrant frequent monitoring (see Significance and Progression). Frequently asked questions from owners of dogs with asymptomatic chronic mitral valve insufficiency are if exercise should be restricted and if dietary measures should be instituted. At present there is little evidence-based information concerning the effects of exercise or diet on the progression of chronic mitral valve insufficiency in dogs. Dogs with mild chronic mitral valve insufficiency do not need any dietary or exercise restriction. However, from the pathophysiologic standpoint, strenuous exercise or diets with high sodium content should be avoided in progressed chronic mitral valve insufficiency as this may promote pulmonary edema. Furthermore, it is the authors’ experience that dogs with advanced asymptomatic chronic mitral valve insufficiency usually tolerate comparably long walks at their own pace and do better if obesity is avoided.

Patients with Left Mainstem Bronchial Compression Without Pulmonary Congestion and Edema

Severe left artial enlargement may produce coughing even in the absence of pulmonary congestion and edema by compression of the left mainstem bronchi, which may be identified on the lateral radiograph. With significant coughing, therapy is aimed at suppression of the cough reflex or reduction of the influence of the underlying cause for the compression, the left atrial enlargement. Cough suppressants such as butorphanol (0.55 to 1.1 mg/kg q6-12h PO), hydrocodone bitartrate (0.22 mg/kg q4-8h PO), or dextromethorphan (0.5 to 2 mg/kg q6-8h PO) may alleviate the coughing in some cases. Dogs with evidence of concurrent tracheal instability or chronic small airway disease may improve with a bronchodilator, or a brief course of glucocorticoids. Different xanthine derivatives, such as aminophylline (8 to 11 mg/kg q6-8h) and theophylline (Theo-Dur (sustained duration) 20 mg/kg q12h PO, Detriphylline (Choledyl) (sustained action) 25 to 30 mg/kg q12h PO), are commonly used bronchodilators, although the efficacy of these drugs varies considerably between individuals. Beta 2-receptor agonists such as terbutaline and albuterol should be used with caution in chronic mitral valve insufficiency dogs, as these drugs may produce unwanted elevation in heart rate and contractility as a consequence of myocardial beta 2-receptor stimulation. A reduction of left atrial size may be obtained either by reduction of the regurgitation or by reduction of pulmonary venous pressure. Regurgitation can be decreased by reducing aortic impedance with an arterial dilator or by contracting blood volume with a diuretic.

ACE-inhibitors or a directly acting arterial vasodilator, such as hydralazine, may reduce systemic arterial resistance. The ACE-inhibitors are substantially weaker arterial vasodilators than hydralazine. Side effects of ACE-inhibitors are infrequent, but monitoring of renal function and serum electrolytes, particularly potassium, may be indicated.

Hydralazine has been widely used in patients with chronic mitral valve insufficiency at an initial dosage of 0.5 mg/kg every 12 hours PO. The dosage is increased at daily to weekly intervals to an appropriate maintenance dose of 1 to 2 mg/kg every 12 hours PO, or until hypotension develops, detected either by blood pressure measurements or by clinical signs. Clinical hypotension is defined as a mean arterial blood pressure of less than 50 to 60 mm Hg or a systolic blood pressure below 90 mm Hg. Reflex tachycardia may develop in response to hypotension, and gastrointestinal problems are sometimes observed. In tachycardia, digoxin may be considered in order to limit the resting heart rate. As a consequence of hypotension, hydralazine may induce fluid retention and thereby is needed in the form of a diuretic. Patients that receive hydralazine should routinely be monitored, including having the owner check the heart rate at home and having renal function assessed periodically. Diuretic mono-therapy may be considered to decrease the mitral regurgitation by contracting the blood volume and thereby the left ventricular size. However, diuretics activate the renin-angiotensin-aldosterone system (RAAS), and in the long term may cause electrolyte disturbances. Accordingly, these drugs are often reserved for patients with signs of pulmonary congestion and edema or patients in which cough suppressants, glucocortocoids, and vasodilators have failed to alleviate clinical signs.

Patients with Syncopes but Without Pulmonary Congestion and Edema

With advancing chronic mitral valve insufficiency it is not uncommon that episodes of syncope develop in otherwise asymptomatic dogs (see Clinical Signs). These episodes vary in frequency from isolated to multiple events every day. In dogs with chronic mitral valve insufficiency with syncope, it is important to ascertain that the patient is actually fainting and not suffering from neurologic or metabolic disease. Furthermore, it is important to rule out the presence of congestive heart failure or a bradyarrhythmia such as third degree AV-block or a tachyarrhythmia such as atrial fibrillation. Although ventricular tachyarrhythmias do occur in dogs with advanced chronic mitral valve insufficiency (CMVI), supraventricular tachyarrhythmia is far more common. Typically, the 24-hour (Holter) ECG shows episodes of a rapid supraventricular rhythm immediately followed by a bradycardia during which the dog faints. Management of these dogs often includes digoxin to control the supraventricular tachyarrhythmia. In fact, the frequency of syncopes may often be controlled at lower doses, such as 50%, of digoxin than the recommended dose (which is 0.22 mg/m2 q12h PO).The place for beta-blockers in controlling episodes of fainting in chronic mitral valve insufficiency dogs is not clear. Reports indicate positive results of carvedilol in some dogs. However, beta-blockers may reduce myocardial performance and some chronic mitral valve insufficiency dogs do not tolerate this type of therapy.

Patients Unth Pulmonary Edema Secondary To Chronic Mitral Valve Insufficiency

Considering the pathophysiology of chronic mitral valve insufficiency (CMVI), therapy should be directed toward (1) reduction of the venous pressures to alleviate edema and effusions, (2) maintainance of adequate cardiac output to prevent signs of weakness, lethargy and prerenal azotemia, (3) reduction of the cardiac workload and regurgitation, and (4) protection of the heart from negative long-term effects of neurohormones. Cases with mild pulmonary edema may be managed on an outpatient basis with regular re-examinations. Cases with moderate to severe pulmonary edema may need intensive care, including cage-rest and sometimes oxygen supplementation.

Mild to Moderate Heart Failure

Patients with mild to moderate heart failure usually present with cough, tachypnea, and dyspnea. It is not common for an untreated dog in congestive heart failure to present initially with isolated significant ascites. Signs of congestive heart failure are usually present on thoracic radiographs as pulmonary venous congestion and increased pulmonary opacity. In some cases, it may be difficult to appreciate mild edema owing to obesity, chest conformation, underinflated lungs, or presence of age-related changes. Radiographs from the patient obtained before the onset of clinical signs may be helpful for comparison. Dogs with mild to moderate heart failure should be treated. Treatment can often be managed on an outpatient basis and should include a diuretic, such as furosemide, and an ACE-inhibitor. The place of digoxin and other positive inotropes are more controversial for treating dogs with mild to moderate heart failure (see below). The dosage of furosemide should preferably be based on clinical signs rather than radiographic findings. A patient may breathe with ease even in the presence of radiologic signs of interstitial edema, or vice versa. The usual course of treatment of a case with mild to moderate heart failure is an initial intensive treatment with furosemide (2 to 4 mg/kg q8-12h) for 2 to 3 days, after which the dosage of the diuretic is decreased to a maintenance level, such as 1 to 2 mg/kg every 12 to 48 hours or lower. More severe cases of heart failure may require higher dosages. It is important to use an appropriate dosage of diuretic to relieve clinical signs but to avoid an unnecessarily high maintenance dosage. Overzealous use of diuretics may lead to weakness, hypotension, syncope, aggravation of prerenal azotemia, and acid-base and electrolyte imbalances. Often the owner can be instructed to vary the dosage, within a fixed dose range, according to the need of the dog.

The dosage of ACE-inhibitor (e.g., enalapril, benazepril, lisinopril, ramipril, and imidapril) is usually fixed and depends on the specific ACE-inhibitor used. ACE-inhibitors are indicated in advanced chronic mitral valve insufficiency with heart failure in combination with diuretics, because dogs in large placebo-controlled clinical trials receiving an ACE-inhibitor have been shown to have less severe clinical signs of disease, better exercise tolerance, and live longer than those not receiving an ACE-inhibitor. In the dose range that is recommended for use in dogs and cats, the vasodilating actions of the drugs are not prominent and side effects associated with hypotension, such as fainting and syncope, are rare. A reason for this may be that the short-term effects of ACE-inhibitors on the circulation are dependent on the activity of the RAAS prior to administration of the drug, the higher activity the more pronounced effect of the drug. In combination with diuretics, such as furosemide, the ACE-inhibitors have synergistic effect with the diuretic by counteracting the reflectory stimulation of RAAS that occurs in diuretic therapy. Thus they decrease the tendency for fluid retention and counteract a peripheral vaso-constriction and other negative effects on the heart.

Digoxin is controversial in treating dogs with chronic mitral valve insufficiency (CMVI). There is generally a lack of scientific evidence supporting the use of digoxin. Many cardiologists, however, initiate digoxin therapy when signs of heart failure first appear. Although digoxin is a comparably weak positive inotrope and myocardial failure may not be a prominent feature of chronic mitral valve insufficiency until progressed stages, digoxin has a place in heart failure therapy by reducing reflex tachycardia, by normalizing baroreceptor activity and by reducing central sympathetic activity. Thus digoxin may be useful to reduce the heart rate, such as when hydralazine is administered, or in supraventricular tachycardia such as atrial fibrillation, and to abolish or limit the frequency of syncope (see above).

The place for a positive inotrope in the management of chronic mitral valve insufficiency is controversial, since in small dogs signs of left-side heart failure usually precede overt myocardial failure. Nevertheless, the combined calcium sensitizer/PDE III inhibitor pimobendan is now approved for veterinary use in dogs with dilated cardiomyopathy and chronic mitral valve insufficiency in many European countries, Canada, and Australia at a dose of 0.25 mg/kg every 12 hours PO. Data from controlled clinical trials of pimobendan in veterinary patients is available, although its efficacy is less documented in chronic mitral valve insufficiency than in DCM. Recendy, two controlled clinical trials (the PITCH trial and a recendy completed study from UK) were presented (unpublished), The results indicate that dogs with chronic mitral valve insufficiency receiving pimobendan as adjunct therapy to diuretics show less severe signs of heart failure and are less likely to die or reach the treatment failure end-point than those receiving an ACE-inhibitor and diuretics. Many practitioners using pimobendan have experienced a dramatic improvement in overall clinical status in some CVMI dogs, even in dogs without overt myocardial failure. The reason for this may be that pimobendan, in addition to being a positive inotrope, has arterial vasodilating properties and differs from the pure phosphodiesterase III antagonists (such as milrinone) in that it increases myocardial contractility with minimal increase in myocardial energy consumption. Furthermore, positive inotropes may theoretically reduce the mitral regurgitation by decreasing the size of the left ventricle and the mitral valve annulus through a more complete emptying of the left ventricle. However, the increased contractility may also theoretically lead to an increased systolic pressure gradient across the mitral valve and thereby generate increased regur-gitation in some cases with high peripheral vascular resistance and increase the risk for chordal rupture in affected dogs. Therefore some cardiologists initiate pimobendan as adjunct therapy to other heart failure treatment in chronic mitral valve insufficiency dogs only when echocardiographic evidence of reduced myocardial performance (increased left ventricular end-systolic dimension) is evident. Whether or not this treatment strategy is the optimal use of calcium sensitizers has not been evaluated. Some cases of chronic mitral valve insufficiency with evidence of myocardial failure have evidence of disseminated myocardial micro-infarctions, most commonly as a consequence of widespread arteriosclerosis. Some of these patients might benefit from prophylactic antithrombotic and antiplatelelet therapy, although this has not been evaluated in veterinary medicine.

The way dogs with mild to moderate heart failure are managed after initiation of therapy varies. Typically, the dog is re-examined after 1 to 2 weeks of therapy, if the dog is managed on an outpatient basis, to monitor therapeutic outcome and to establish a suitable maintenance dosage of diuretic. Should the treatment response be satisfactory after this visit, dogs may often be managed by phone contacts and re-examinations every 3 to 6 months. More severe cases may require more frequent monitoring of the disease. In areas with a seasonal climate it may be valuable to re-examine the dog before the temperature increases and instruct the owner to avoid high ambient temperatures. The use of low-sodium diets as complementary therapy in heart failure is controversial. Currently, there are no clinical studies to support that they are beneficial in managing heart failure in dogs and cats. However, dogs with symptomatic chronic mitral valve insufficiency should avoid excessive intake of sodium. Dogs that are stable on their heart failure therapy usually tolerate walks at their own pace, but strenuous exercise should be avoided.

Recurrent Heart Failure

Once an appropriate maintenance dosage of furosemide has been set in a chronic mitral valve insufficiency patient with decompensated heart failure, the dosage has to be gradually increased, often over weeks or years. Reasons for increasing the dosage often include recurrent dyspnea caused by pulmonary edema or the development of ascites. Severe ascites, which compromises respiration, may require abdominocentesis. Many chronic mitral valve insufficiency cases with less severe ascites respond to an increased dose of diuretics. Even in case of abdominocentesis, the diuretic dosage should be increased as the ascites will re-occur without changed medication after evacuation. When the dosage of furosemide has reached a level of approximately 4 to 5 mg/kg every 8 to 12 hours, sequential blocking of the nephron should be considered by adding another diuretic. The drug of choice is spironolactone (1 to 3 mg q12-24h PO) which is an aldosterone antagonist and a potassium-sparing diuretic. A thiazide, such as hydrochlorothiazide (2 to 4 mg/kg q12h PO), or triamterene (1 to 2 mg/kg q12h PO) or amiloride (0.1 to 0.3 mg/kg q24h PO), may also be considered. The documentation of triamterene and amiloride in veterinary medicine is limited.

Because the furosemide treatment precedes and is used concomitantly with these drugs, the risk of hyperkalemia is low, even when they are added to a patient that is currently treated with an ACE-inhibitor. The risk of inducing prerenal azotemia, hypotension, and acid-base and electrolyte imbalances increases with the intensity of the diuretic treatment. However, the practitioner usually has to accept some degree of these disturbances when treating a patient with heart failure and, although common, they seldom result in clinical problems. A calcium senzitizer (pimobendan) is often introduced in cases with recurrent heart failure, as echocardiographic evidence of systolic dysfunction often has developed (see above).

Severe and Life-Threatening (Fulminant) Heart Failure

The causes of acute severe heart failure are often a ruptured major tendinous chord, development of atrial fibrillation, undertreatment of existing heart failure, or intense physical activity, such as chasing birds or cats, in the presence of significant chronic mitral valve insufficiency (CMVI). Patients with severe heart failure have radio-graphic evidence of severe interstitial or alveolar edema and have significant clinical signs of heart failure at rest. They are often severely dyspneic and tachypneic and have respiratory rates in the range of 40 to 90. They may cough white or pink froth, which is edema fluid. These dogs require immediate hospitalization and aggressive treatment. However, euthanasia should also be considered, if the dog is already on high doses of diuretics and other heart failure therapy, owing to the poor long-term prognosis. It is important not to stress dogs with severe or fulminant heart failure as stress may lead to death. Therefore thoracic radiographs and other diagnostic procedures may have to wait until the dog has been stabilized.

Dogs with significant dyspnea benefit from intravenous injections of furosemide at a relatively high dose (4 to 6 mg/kg q2-6h IV). The furosemide may be administered intramuscularly should placement of an intravenous catheter not be possible. Dogs with fulminant pulmonary edema may require Herculean furosemide doses at 6 to 8 mg/kg every 2 to 8 hours IV over the first 24 hours. The exact dosage of furosemide depends not only on severity of clinical signs but also on whether or not the dog is already on oral furosemide treatment. Oxygen therapy is always beneficial in hypoxemic patients and it can preferably be administered using an oxygen cage provided that the temperature can be controlled inside the cage. Nasal inflation or a facial mask may also be used provided that the animal accepts them without struggle. Once the dog has received furosemide and oxygen treatment, an arterial vasodilator and a positive inotrope may be considered to stabilize the patient.

Commonly used vasodilating agents are hydralazine per os or intravenous nitroprusside (2.0-10 mg/kg/min). Of these two vasodilators, hydralazine is most commonly used. Owing to the severity of heart failure, dogs without previous vasodilating therapy may receive an initial dose of hydralazine of 1 to 2 mg/kg PO. Titration of the hydralazine dosage as described above is indicated in dogs already on an ACE-inhibitor and blood pressure should be monitored to detect hypotension. Nitroprusside can only be administered as an intravenous infusion, which requires an intravenous catheter. This potent vasodilator has actions on both the venous and arterial circulation. However, it is not easy to control the effects of nitroprusside and the dosage has to be titrated under careful blood-pressure monitoring to avoid serious hypotension and to ensure efficacy. These disadvantages have prevented nitroprusside from being a commonly used arterial vasodilator.

A positive inotrope such as dobutamine, or more commonly the calcium-sensitizer pimobendan (0.25 mg/kg q12h PO), may be considered to stabilize the patient with fulminant heart failure. Pimobendan may be administered together with furosemide without any arterial vasodilator as the drug has vasodilating properties itself The dose of any concurrently administered arterial vasodilator has to be adjusted. Dobutamine is administered as a constant infusion usually in combination with nitroprusside. One problem with dobutamine that limits its use is that the patient needs to be weaned from IV to oral therapy within 1 to 2 days.

Patients with severe or fulminant heart failure need frequent initial monitoring of the respiratory rate because it reflects the clinical response to the furosemide treatment. Significandy decreased respiratory rate within the first hours indicates successful therapy, whereas absence of change indicate that furosemide is required at a higher dose or more frequently. Once the respiratory rate has decreased, the dose of furosemide may be reduced according to the status of the animal and clinical judgment. Abnormal laboratory findings such as pre-renal azotemia, electrolyte imbalances and dehydration are common after high doses of furosemide. Again, these abnormalities are seldom a clinical problem and the laboratory values often tend to shift towards normal with clinical improvement and as the dog starts to eat and drink. Dehydration is usually not severe even after intensive furosemide treatment and intravenous rehydration should be performed slowly and with caution in cases where it is needed, as the volume challenge may produce pulmonary edema.