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

Arterial thromboembolism in the cat

Cats with any form of cardiomyopathy have a predilection to form intracardiac thrombi in the left atrium; the incidence is highest in cats with hypertrophic cardiomyopathy. These thrombi often become lodged at the bifurcation of the iliac arteries; less frequently they may occlude the brachia!, coeliac or renal arteries.


Altered blood flow and vascular stasis predispose to thrombus formation. Localized release of vasoactive substances such as serotonin and thromboxane at the site of vascular occlusion result in vasoconstriction of the collateral blood supply adjacent to the occluded vessel. Moreover, the release of serotonin induces platelets to aggregate which further potentiates clot formation. Occlusion at the iliac bifurcation (a so called *saddle* thrombus) results in ischaemic damage to the muscles and nerves of both hind limbs (ischaemic neuromyopathy).

Clinical signs

Iliac thrombosis is characterized by the sudden onset of crying and hindlimb paresis which results in dragging of one or both hind limbs (occlusion of a brachial artery may cause similar signs in a fore limb). The cat may present with acute dyspnoea and mouth breathing and the mucous membranes may appear cyanotic (particularly if a pulmonary artery is thrombosed). The affected muscles become firm and painful to touch after 24 hours. One or both femoral pulses may be absent and the paws and distal limbs are hypothermic (pink pads may appear pale).


Diagnosis is usually based on the history and clinical signs. Since most cases of iliac thrombosis are associated with cardiomyopathy echocardiography should be performed as soon as the cat is stabilized. Non-selective angiocardiography may be helpful to determine the extent of the thrombosis and also the integrity of the collateral blood supply. Acute muscle damage results in increased plasma concentrations of aspartate aminotransferase (AST) and creatine kinase (CK). Urea and creatinine concentrations may increase after embolization of a renal artery.

Since the clinical signs of iliac thrombosis resemble those of lower motor neurone paralysis, spinal cord lesions, for example, acute spinal cord trauma, intervertebral discprotrusion (rarein the cat) or haemorrhage, and intravertebral tumours (lymphosarcoma) should be considered as differential diagnoses.

Arterial thromboembolism: Treatment

Treatment should he directed at alleviating signs associated with the thrombus as well as the underlying cardiac disorder responsible for its formation. Aspirin (25 mg kg-1 body weight per os every 72 h) should be given to inhibit platelet function. One study showed that the administration of aspirin resulted in significant preservation of collateral blood supply in eats after experimental induction of iliac thrombosis and a shortening of the recovery period. However, there is evidence to suggest that aspirin is not effective in preventing further embolic episodes. The use of acepromazine (0,2-0.4 mg kg-1 bodyweight subcutaneously three times daily) has been advocated for its vasodilator properties. Heparin may be given to prevent further activation of the coagulation process (an initial intravenous dose of 1000 USP followed 3 h later by 50 USP units kg-1 body weight subcutancously and thereafter 50 USP units kg-1 bodyweight every 6-8 b). Regular daily monitoring of activated partial thromboplastin lime (APTT) is advised so that the APTT is not prolonged by more than 1.5-2,0 times the preheparin baseline values. Morphine (0.1 mg kg-1 bodyweight) can be given as an analgesic for the first 24-48 h.

The use of the serotonin antagonist, cyproheptadine, and thrombolvtic agents such as streptokinase, urokinase and tissue plasminogen activator (t-PA) have yet to be fully evaluated and to date the results have been equivocal.


The prognosis is at best guarded. Many animals fail to respond to medical management or succumb to the underlying cardiomyopathy. Recurrence is common. Spontaneous recanalization of the clot may occur with or without drug therapy after 2-4 days. Many cats are left with signs of residual peripheral nerve damage. Full recovery may take up to 4-6 weeks.

Veterinary Medicine


Canine heart worm disease caused by Dirofilaria immitis is endemic in most temperate and tropical coastal zones of the world (United States. Japan and Australia especially). Heartworm disease is occasionally diagnosed in imported dogs in the United Kingdom. Affected animals are often between 4 and 7 years of age although the condition has been diagnosed in animals less than one year of age.

Life cycle of Dirofilaria immitis

When a mosquito bites an infected dog circulating microfilaria (first stage larvae) are ingested and develop into third stage (L3) larvae which migrate to the mouth parts of the mosquito. The third larval stage of the heartworm (Dirofilaria immitis) stage enters the subcutaneous tissues of the host via a bite from an infected mosquito. Young adult worms (L5 stage) reach the right side of the heart by 90-100 days postinfection. There is a prepatent time of approximately 6 months before microfilaria appear in the circulation. Occult infections occur where there is an absence of circulating microfilaria.

Pathophysiology of heartworm disease

Adult worms live most commonly in the right ventricle, main pulmonary artery and parenchymal pulmonary arteries. As the number of heart-worms increases they enter the right atrium and eventually migrate into the caudal vena cava. Large numbers of worms may obstruct the caudal vena cava and flow of blood to the right atrium (vena caval syndrome).

Adult worms initiate a parasite-host reaction which damages the pulmonary artery endothelium. Histologically this reaction is characterized by the proliferation of smooth muscle cells on the endothelial surface of the vessels. Circulating antibodies trap the microfilaria within the pulmonary arteries which results in pulmonary infarction and areas of consolidation around the affected vessels. Alveolar hypoxia increases pulmonary vascular resistance and leads to pulmonary hypertension. Pulmonary hypertension results in increased right ventricular afterload, right ventricular hypertrophy and eventually signs of right-sided heart failure (cor pulmonale).

Clinical signs

The clinical signs of heartworm disease, once apparent, are usually severe and progress rapidly. Damage to the pulmonary arteries results in coughing, haemoptysis, dyspnoea and decreased exercise tolerance. There is a rapid loss of body condition and pulmonary hypertension leads to right-sided heart failure. Tricuspid valve murmurs may be heard due to mechanical interference with valvular function by the adult worms.

Some infected dogs show few if any clinical signs. Those with occult heartworm disease develop an allergic pneumonitis characterized by severe coughing and dyspnoea. Two conditions which may have an immune-mediated pathogenesis, eosinophilic granulomatosis and pulmonary infiltrates with eosinophilia (eosinophilic pneumonia), may also occur in association with heart-worm disease. Severe pulmonary artery disease may result in thromboembolic complications and thrombocytopenia especially after adulticide therapy.

Haemolysis and haemoglobinuria may occur when a large number of worms obstruct the caudal vena cava and result in fragmentation of red cells. Dogs with the caval syndrome become severely dyspnoeic and show signs of acute hypotension (tachycardia, pale mucous membranes and prolonged capillary refill time).

Electro cartography

Electrocardiographs signs of right ventricular enlargement may be evident especially in dogs showing signs of right-sided heart failure.

Radiographic findings

Radiographic changes develop early during the course of heartworm infection. Typical abnormalities include right ventricular enlargement and a bulging pulmonary artery segement with enlarged lobar pulmonary arteries. As the disease progresses the peripheral pulmonary arteries become truncated and tortuous especially in the caudal lung lobes. Patchy alveolar densities may be apparent especially after adulticide therapy.

Clinicopathological findings

Eosinophilia often accompanied by basophilia are the most consistent haematological abnormalities, occurring once die young adult worms enter the circulation. A mild regenerative anaemia may be present and neutrophilia may occur following aduhicide treatment. Platelet numbers are often reduced as a result of increased consumption in response to endothelial damage. Liver enzymes may be increased especially if signs of right-sided cardiac failure are present; total plasma proteins may also be increased due to an increase in the globulin fraction. Proteinuria occurs in 20-30% of cases; some animals develop a glomerulonephropathy and nephrotic syndrome, and become hypoalbuminaemic.

Diagnosis of Dirofilariasis

The presence of microfilaria on a peripheral blood film implies the presence of adult worms. Dirofilaria immitis microfilaria should be differentiated from those of Dipetalonema reconditum and other Dipetalonema species which cause asymptomatic infections in dogs. This can be done by examining the acid phosphatase staining pattern of filter-treated micro-filariae. The blood of young dogs from endemic areas should be screened annually for the presence of microfilaria using a Knott’s test. With occult infections, no circulating microfilaria are present and diagnosis is dependent on the detection of appropriate radiographic abnormalities and the results of other serodiagnostic tests.

An indirect fluorescent antibodv test detecting antibodies to microfilarial antigens is useful in the diagnosis of occult heartworm disease. An ELISA test for detecting antibodies against adult worms has proved to be less satisfactory because of the high incidence of false positive results, although a negative ELISA result can be regarded as reliable evidence that occult heart-worm disease is not present. More recently, ELISA tests using monoclonal antibodies against circulating adult antigens have been developed which appear to be more sensitive and specific than tests which detect adult antibodies.

Dirofilariasis: Treatment

Adulticide therapy

Thiacetarsamide (22 mg kg-1 body weight intravenously twice daily for two days) eliminates a high percentage of the adult heart worms (young female heart worms are often resistant). The second dose should be given not more than 10 hours after the first. Treatment with thiacetarsamide should be delayed in dogs with radiographic signs of severe pulmonary artery disease since such animals are at risk from developing thromboembolic complications and thrombocytopenia post-treatment. Toxic reactions to thiacetarsamide occasionally occur; these include anorexia, vomiting, depression, fever, diarrhoea and the presence of tubular casts in the urine. Adulticide treatment is usually followed 4-6 weeks later by the administration of a microfilaricide. The benefits of giving a microfilaricide three weeks before treatment with thiacetarsamide are questionable.

Levamisole has been used as an alternative adulticide drug but is less effective than thiacetarsamide. It is more effective as a microfilaricidal drug but toxic side effects (vomiting and CNS signs) are common.

The prophylactic use of aspirin to combat the potential thromboembolic complications has been questioned. Recent studies have shown that even doses of aspirin greater than 50 mg kg-1 in some dogs will not prevent thromboembolism or imimal hyperplasia associated with heart worm emboli.

Corticosteroids are indicated if there is evidence of an eosinophilic pulmonary infiltrate. Heparin has been recommended for dogs showing signs of chronic or low-grade disseminated intravascular coagulation (DIC).

Microfilaricide treatment

Levamisole, milbemycin and ivermectin are available for use as microfilaricides (the last two can also be used prophylactically). The American Heartworm Society currently recommends that cither ivermectin (50 μg kg-1) or milbemycin (500 μg kg-1) be given 3-4 weeks after treatment with adulticide. Treatment of dogs with large numbers of microfilaria may lead to circulatory collapse due to rapid death of the microfilaria. Dogs should therefore be observed for 6-8 h after treatment. The use of ivermectin and milbemycin in collies and collie cross breeds has been associated with anaphylactic reactions and, in some cases, death; although both the microfilaricidal and the preventative doses of these drugs are reportedly safe in susceptible collies other drugs, for example levamisole (10 mg kg-1 day-1 for 7 days) have been recommended for this breed.

Prevention of heartworm disease

Chemoprophylaxis should be initiated 2-3 weeks after administration of a microfilaricide providing no microfilariae are detected in the blood; if microfilariae are still present microfilaricidal treatment should be repeated). In endemic areas, either ivermectin (6-12 μg kg-1) or milbemycin (500-999 μg kg-1) can be administered once a month. Young pups can be treated prophylactically from 6-8 weeks of age onwards. Although both drugs can be safely given to dogs which may already have circulating microfilariae, they only kill D. immitis larvae during the first six weeks of their development. Both drugs are also known to induce sterility in adult worms there-fore dogs greater than 6 months of age on monthly preventative treatment should be tested for antigen to detect occult infections which may develop within 6 months of starting monthly macrolide administration.

Veterinary Medicine

Cor pulmonale

Cor pulmonale is the term used to describe the alterations in the structure or function of the right ventricle which may be induced by pulmonary hypertension secondary to primary lung disease.

Pathophystology of cor pulmonale

Cor pulmonale may be acute or chronic. Alveolar hypoxia and hypoxaemia, respiratory acidosis and hypercapnoea combine to increase pulmonary vascular resistance. Pulmonary hypertension results in acute or chronic right ventricular pressure overload, right ventricular hypertrophy and eventually signs of right-sided failure.

Acute cor pulmonale caused by pulmonary thromboembolism or heartworm disease is of ten fatal and in most cases may not be diagnosed. Pulmonary thromboembolism can occur as a complication of chronic renal disease (especially glomerulo-nephropathy), hyperadrenocorticism, immune-mediated haemolytic anaemia and pancreatitis.

Chronic cor pulmonale may occur as a sequel to chronic obstructive pulmonary disease. It has been associated with chronic bronchitis, bronchiectasis, pulmonary fibrosis, infiltrative lung disease (for example neoplasia), chronic partial upper airway obstruction due to collapsing trachea, laryngeal paralysis or elongation of the soft palate, and heartworm disease.

Clinical signs of cor pulmonale

Animals with acute cor pulmonale due to pulmonary thrombosis present with severe dyspnoea and are often cyanotic. The mortality rate is high. The clinical signs of chronic cor pulmonale depend on the nature and severity of the underlying respiratory disorder. A chronic cough and / or wheezing is common in dogs with chronic bronchitis, bronchiectasis and collapsing trachea; dogs with chronic partial upper airway obstruction due to an elongated soft palate or laryngeal dysfunction may become progressively dyspnoeic with signs of inspiratory stridor / stertor. Failure to treat the underlying problem may lead to signs of right-sided congestive heart failure.


Pulmonary hypertension and resultant right ventricular hypertrophy may result in tall P waves (right atrial enlargement) and deep Q or S waves in leads I. II. III and aVF (right ventricular enlargement). The mean electrical axis may shift to the right and myocardial hypoxia may result in ST segment depression.

Radiographic findings

Acute pulmonary thromboembolism results in pulmonary hypoperfusion and lobar hyperlucency. Pulmonary vessels may appear truncated especially towards the periphery. A minimal amount of pleural fluid may be present. Right ventricular enlargement is a feature of chronic cor pulmonale and many animals will show concurrent radiographic changes consistent with chronic lung disease, for example a diffuse bronchial and / or interstitial pattern or bronchiectasis.

Cfinicopathological findings

Blood gas analysis

Hypoxia (PaO2 <80 mm Hg), hypercapnoea (PaCO2 >40 mm Hg) and acidosis (pH <7.4) reflect the severity of the underlying pulmonary pathology. Chronic hypoxia occasionally results in secondary polycythaemia. Animals with acute pulmonary thromboembolism may become thrombocytopenic and show other laboratory evidence of disseminated intravascular coagulation. Pulmonary hypertension and right ventricular pressure overload result in an increase in central venous pressure.

In addition to the above, diagnostic investigations such as bronchoscopy and tracheal or bronchoalveolar lavage should be performed where appropriate to establish the nature of the underlying respiratory disorder responsible for the cardiac changes.

Cor pulmonale: Treatment

Treatment of the underlying pulmonary condition should be instituted as quickly as possible. Acute pulmonary thromboembolism should be treated with cage rest, oxygen and antithrombotic drugs such as heparin and aspirin. The prognosis is generally poor if signs of right-sided heart failure are present.

Veterinary Medicine

Tetralogy of Fallot

The four components of tetralogy of Fallot are (1) pulmonic stenosis (valvular, infundibular or both), (2) high ventricular septai defect, (3) compensatory right ventricular hypertrophy (secondary to pulmonic stenosis) and (4) an overriding or dextraposed aorta which means the aorta may arise from both ventricles or from the right ventricle alone.


The haemodynamic abnormalities associated with tetralogy of Fallot depend largely on the size of the ventricular septal defect and degree of pulmonic stenosis. Right ventricular systolic pressure increases resulting in a variable degree of right ventricular hypertrophy. A large ventricular septal defect accompanied by a minimal degree of pulmonic stenosis results in a left to right or bidirectional shunt, pulmonary overcireulation and volume overload of the left side of the heart. A minimal amount of venous, non-oxygenated blood enters the systemic circulation via the overriding aorta and therefore cyanosis is not apparent. In comparison, severe pulmonic stenosis and a large ventricular septal defect leads to an increase in pulmonary vascular resistance and the development of a right to left vascular shunt. Hypertrophy of the right ventricular outflow tract and / or hypoplasia of the pulmonary artery may contribute to the pulmonic stenosis. Dogs with severe pulmonary hypertension may develop signs of right-sided heart failure.

Tetralogy of Fallot is more common in smaller breeds of dog (for example English bulldogs, poodles, and terrier breeds); in the keeshond breed tetralogy has a poly genie mode of inheritance.

Clinical signs

Most dogs with tetralogy show clinical signs during the first 6-12 months of life. Clinical signs associated with severe right to left shunts include syncope, cyanosis, and dyspnoea which may be apparent even at rest. Affected dogs often appear severely stunted and show marked exercise intolerance. Chronic hypoxia, due to shunting of unsaturated blood across the ventricular septal defect, may lead to secondary polycythaemia. A systolic murmur, and occasionally a precordial thrill, typical of pulmonic stenosis can often be heard over the left 3rd intercostal space although this may become attenuated as the pressure within the right ventricle equilibrates with that in the left ventricle and blood is shunted preferentially through the aorta.

A harsher holosystolic ‘diagonal-type’ murmur more suggestive of a ventricular septal defect may be detected in cases where the pulmonic stenosis is less severe.


Most cases of tetralogy showing clinical signs have ECG changes consistent with right ventricular enlargement and a right axis shift. Signs of left-sided enlargement may be present in cases with a left to right shunting ventricular septal defect.


The classical features of tetralogy of Fallot are right ventricular enlargement and an enlarged pulmonary artcry segment. Displacement of the aorta may result in a loss of the cranial waist. A right to left shunting ventricular septal defect may result in hyperlucency of the lung fields due to pulmonary hypoperfusion.


Echocardiography can be used to image the high ventricular septal defect, pulmonic stenosis and dextraposirion of the aorta, and to confirm right ventricular hypertrophy. Other findings include reduced left atrial and left ventricular internal dimensions; hypertrophy with flattening or paradoxical motion of the inter -ventricular septum may also be apparent. A non-selective contrast (bubble) study may help to confirm the presence of a right to left shunting ventricular septal defect.

Angiocardiography and intracardiac catheterization

The non-selective injection of contrast via the jugular vein or a selective injection into the right ventricle results in simultaneous opacification of the pulmonary artery and aorta with no apparent left ventricular filling. Post-stenotic dilatation of the main pulmonary art cry is usually evident. Right ventricular pressure increases (normal less than 35 mm Hg) and a systolic pressure gradient develops across the pulmonic valve.

Tetralogy of Fallot: Treatment

Dogs with low pressure gradients across the pulmonic valve (less than 30 mm Hg) and a left to right shunt can be managed conservatively. The prognosis for more severe right to left shunting cases which are cyanotic is generally poor and few animals survive beyond 12-18 months of age. Although definitive surgical correction is only possible with cardiopulmonary bypass, creation of a systemic-pulmonary artery shunt, for example between the aorta and pulmonary artery (Potts anastomosis) or subclavian artery and pulmonary artery (Blalock-Taussig procedure), may increase pulmonary blood flow and systemic oxygenation. Animals which are significantly poly-cythaemic (PCV greater than 0,60 ll-1) may be given aspirin to minimize the risk of thromboembolic complications. The administration of beta-adrenergic blocking drugs has been advocated although their value has not been determined.

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.


Therapy Of Thromboembolic Disease

The management of primary diseases resulting in the development of thromboembolism is discussed in related posts throughout this textbook. Therapy of thromboembolism should be directed toward the underlying disorder whenever possible. Therapeutic strategies for managing thromboembolism include short-term systemic anticoagulation and fibrinolysis followed by long-term antiplatelet or anticoagulant therapy to reduce the risk of rethrombosis.

Supportive Care

General patient care is critical for successful management of thrombosis. Analgesic agents should be considered for acute pain management. Fluid therapy should be administered when indicated to correct acid-base abnormalities and dehydration. Dextrose-containing fluids should be avoided whenever possible because they may cause endothelial damage, further promoting thrombosis. A risk of volume overload exists with heart failure or pulmonary hypertension and fluid therapy must be carefully monitored. Strict cage rest and oxygen therapy are indicated in cases of pulmonary thromboembolism or thrombosis associated with congestive heart failure (CHF).

Acute Anticoagulation

Heparin is the mainstay of acute anticoagulation. Anticoagulants prevent additional clots from forming but do not dissolve clots (see thrombolysis). Coumadin therapy for the long-term control of thrombosis is initiated after adequate hepariniza-tion has been achieved.

Heparin functions as a cofactor with antithrombin III, and together this complex exerts its effect by neutralizing factor X and thrombin. Heparin is inactivated by gastrointestinal (GI) enzymes when given orally and therefore must be administered by injection. Heparin is administered to prolong the baseline activated partial thromboplastin time (aPTT) to 1.5 to 3.0 times the baseline value. Prolongation of the aPTT or activated coagulation time (ACT) does not correlate well with heparin levels in cats and dogs, and measurement of plasma heparin levels may be more useful in monitoring heparin therapy. Although many different heparin doses have been advocated, little clinical data exist concerning efficacy. Doses of heparin required to achieve adequate heparin levels in cats with thromboembolism ranged from 175 U/kg every 6 hours to 475 U/kg every 8 hours, subcutaneously. In normal dogs the dose of heparin required to achieve adequate heparin concentrations was 250 U/kg every 6 hours, subcutaneously. The most common side effect of heparin therapy is hemorrhage. In the event of severe hemorrhage, heparin can be neutralized by protamine sulfate administration.

Low molecular weight (LMW) heparin is being increasingly used. Its anticoagulant effect is limited to blocking the activity of factor X. Because LMW heparin has a lower antithrombin effect than unfractionated heparin, LMW heparin does not markedly influence the PT or aPlT. Measurement of factor X activity has been used to assess the effect of LMW heparin. One advantage of LMW heparin is that it has a lower risk of hemorrhage than conventional hep-arin therapy. The optimal dose of LMW heparin in dogs and cats with thromboembolic disease remains to be determined.

Chronic Anticoagulation

Warfarin (Coumadin) is a vitamin K antagonist inhibiting the synthesis of vitamin K-dependent clotting proteins (prothrom-bin and factors VII, IX and X). In addition, warfarin reduces efficacy of the vitamin K-dependent regulatory proteins C and S. Proteins C and S are anticoagulant factors, and their function is the first to be inhibited by warfarin administration. Therefore heparin and warfarin administration are generally overlapped for 2 to 4 days to prevent a transient hypercoagulable state. Some animals appear to do well with just warfarin. Starting doses for warfarin are 0.25 to 0.5 mg every 24 hours in the cat and 0.1 to 0.2 mg/kg every 24 hours in the dog. Due to the high individual patient variability, close monitoring of PT is essential. Early recommendations were to maintain PT 1.5 times the baseline value, and more recent recommendations suggest attaining an international normalized ratio (INR) of 2:3. INR is calculated by the formula (patient PT/control PT). The ISI is a value specific to the tissue thromboplastin that is used in measuring the PT Coumadin is continued on a long-term basis to prevent recurrent TE. Studies documenting the optimal dose, efficacy, and duration of Coumadin therapy for specific thromboembolic diseases in dogs and cats are unknown.

The use of Coumadin is not without risks. The major risk is fatal hemorrhage, which occurs acutely and unexpectedly. Ideally, pets maintained on Coumadin should live indoors and be well supervised to prevent trauma and to monitor for hemorrhage. Periodic measurement of the PT should be done to ensure adequate dosing. Coumadin interacts with many drugs. The addition of medications to the treatment regimen of a pet on Coumadin should be done cautiously because certain drugs will raise the activity of Coumadin and predispose patients to bleeding. Some of these drugs are phenylbutazone, metronidazole, trimethoprim sulfa, and second- and third-generation cephalosporins. Barbiturates will decrease Coumadin anticoagulant effect. If bleeding complications occur, warfarin therapy is discontinued and administration of vitamin K is recommended.

Antiplatelet Therapy

Antiplatelet drugs have been advocated for long-term management to prevent rethrombosis. These drugs inhibit platelet aggregation and adhesion, preventing the formation of the hemostatic platelet plug. Aspirin inhibits cyclooxygenase, leading to decreased thromboxane A2 synthesis. This renders platelets nonfunctional by preventing their aggregation. Cats lack the enzyme needed to metabolize aspirin (glucuronyl transferase), making them sensitive to aspirin-induced platelet dysfunction. Doses of 0.5 mg/kg every 12 hours in the dog and 25 mg/kg twice weekly in the cat may decrease platelet aggregation. However, rethrombosis generally occurs despite aspirin therapy, although it is not known whether aspirin delays recrudescence. Additional antiplatelet drugs include dipyridamole and ticlopidine. Dipyridamole is thought to inhibit platelet aggregation by inhibition of platelet phospho-diesterase, leading to increased levels of cyclic adenosine monophosphate (cAMP) within platelets. Ticlopidine impairs fibrinogen binding and inhibits platelet aggregation induced by ADP and collagen. The use of these newer compounds has been limited thus far in veterinary medicine.


Thrombolytic agents such as streptokinase, urokinase, and tissue plasminogen activator (tPA) are potent activators of fib-rinolysis. These agents have been used with variable and often limited success in veterinary medicine.

Streptokinase binds plasminogen, and the complex transforms other plasminogen molecules into plasm in. Plasmin then binds to fibrin and causes thrombolysis. Streptokinase binds both free and clot-associated plasminogen. It also degrades factors V, VIII, and prothrombin, resulting in a massive systemic coagulation defect.

Streptokinase has been used to treat aortic thromboembolism (ATE) in cats with varying degrees of success. In one study of 46 cats, 15 were discharged from the hospital after streptokinase therapy with a median survival of 51 days. Reperfusion injury occurred in approximately 35% after thrombolysis, with streptokinase often resulting in fatal hyperkalemia and metabolic acidosis- Eleven of the cats developed clinical hemorrhage after streptokinase therapy. In three cats, hemorrhage was significant enough to require transfusion. Others reported conservative management (treatment of heart failure plus Coumadin or aspirin) of thromboembolism with a hospital discharge rate of 28%, which was similar to cats treated with streptokinase. One recommended dose of streptokinase for dogs and cats with thromboembolism is 90,000 U, intravenously administered over 20 to 30 minutes, followed by a maintenance infusion of 45,000 U for 7 to 12 hours. Infusions may be repeated over a total of 3 days.

Recombinant DNA technology produces t-PA, a serine protease. A complex forms between t-PA and fibrin, and that complex preferentially activates thrombus-associated plasminogen-resulting in rapid fibrinolysis. Life-threatening hemorrhage is the number one side effect. The half-life of t-PA in dogs is 2 to 3 minutes; consequendy, if bleeding occurs, stopping the infusion will result in the drug clearance from the system in 5 to 10 minutes. Because t-PA causes rapid thrombolysis, the risk of reperfusion syndrome and lethal hyperkalemia is substantial. In one report, 50% of cats with thromboembolism died acutely during t-PA therapy, with death attributed to hyperkalemia, severe anemia, and renal hemorrhage.


Treatment And Prevention of Feline Heartworm Disease

The question arises as to whether heartworm prophylaxis is warranted for cats because they are not the natural host and because the incidence is low. Necropsy studies of feline heartworm infection in the Southeast have yielded a prevalence of 2.5% to 14%, with a median of 7%. When considering the question of institution of prophylaxis, it is worth considering that this prevalence approximates or even exceeds that of feline leukemia virus (FeLV) and feline immunodeficiency virus (FTV) infections. A 1998 nationwide antibody survey of over 2000 largely asymptomatic cats revealed an exposure prevalence of nearly 12%. It is also noteworthy that, based on owners’ information, nearly one third of cats diagnosed with heartworm disease at NCSU were housed solely indoors. Lastly, the consequences of feline heartworm disease are potentially dire, with no clear therapeutic solutions. Therefore the author advocates preventative therapy in cats in endemic areas. Three drugs with FDA approval are marketed for use in cats (Table Comparison of Spectra ofMacrolides Currently in Use in Cats). Ivermectin is provided in a chewable formulation, milbemycin as a flavored tablet, and selamectin (a broad-spectrum parasiticide) comes in a topical formulation. The spectrum and the formulation of these products varies; hence the clients’ individual needs are easily met in most cases (Table Comparison of Spectra ofMacrolides Currently in Use in Cats).

Comparison of Spectra ofMacrolides Currently in Use in Cats

Drug Heartwotm prevention Hookworms Whipworms Roundworms Tapeworms Fleas & Eccs Ticks Sarcoptes Ear Mites
Ivermectin (chewable) + +              
Milbemycin (flavored tablet) + +   +          
Selamectin (topical) + +   +   +/+ + + +

Because the vast majority of cats are amicrofilaremic, microfilaricidal therapy is unnecessary in this species. The use of arsenical adulticides is problematic. Thiacetarsemide (sodium caparsolate), if available, poses risks even in normal cats. Turner, Lees, and Brown reported death due to pulmonary edema and respiratory failure in 3 of 14 normal cats given thiacetarsemide (2.2 mg/kg twice over 24 hours). Dillon and colleagues could not confirm this acute pulmonary reaction in 12 normal cats receiving thiacetarsemide, but one cat did die after the final injection. More importantly, a significant, though unquantified, percentage of cats with HW1 develop pulmonary thromboembolism (PTE) after adulticidal therapy. This occurs several days to 1 week after therapy and is often fatal. In 50 cats with HWI, seen at NCSU, 11 received thiac-etarsemide. There was no significant difference in survival between those receiving thiacetarsemide and those receiving symptomatic therapy.

Data on melarsomine in experimental (transplanted) heartworm infection in cats are limited and contradictory. Although an abstract report exists in which one injection (2.5 mg/kg; one half the recommended canine dose) of melarsomine was used in experimentally infected cats without treatment-related mortality, the worm burdens after treatment were not significantly different from those found in untreated control cats. Diarrhea and heart murmurs were frequently noted in treated cats. A second abstract report, using either the standard canine protocol (2.5 mg/kg twice over 24 hours) or the split dose (one injection, followed by two injections, 24 hours apart, in 1 month) described in posts, gave more favorable results. The standard treatment and split-dose regimens resulted in 79% and 86% reduction in worm burdens, respectively, and there were no adverse reactions. Although promising, these unpublished data need to be interpreted with caution because the transplanted worms were young (<8 months old and more susceptible), and the control cats experienced a 53% worm mortality (average worm burden was reduced by 53% by the act of transplantation). Additionally, the clinical experience in naturally infected cats has been generally unfavorable, with an unacceptable mortality. Because of the inherent risk, lack of clear benefit, and the short life expectancy of heartworms in this species, this author does not advocate adulticidal therapy in cats. Surgical removal of heartworms has been successful and is attractive because it minimizes the risk of thromboemboli. The mortality seen in the only published case series was, unfortunately, unacceptable (two of five cats). This procedure may hold promise for the future, however.

Cats with heartworm infection should be placed on a monthly preventa-tive and short-term corticosteroid therapy (prednisone at 1 to 2 mg/kg every 48 hours, three times a day) used to manage respiratory signs. If signs recur, alternate-day steroid therapy (at the lowest dose that controls signs) can be continued indefinitely. For embolic emergencies, oxygen, corticosteroids (dexamethasone at 1 mg/kg intravenously or intramuscularly, or prednisolone sodium succinate at 50 to 100 mg intravenously/cat), and bronchodilators (aminophylline at 6.6 mg/kg intramuscularly every 12 hours, theophylline sustained release at 25 mg/kg orally, or terbutaline at 0.01 mg/kg subcutaneously) may be used. Bronchodilators have logic, based on the ability of agents, such as the xanthines (aminophylline and theophylline), to improve function of fatigued respiratory muscles. In addition, the finding of hyperinflation of lung fields may indicate bronchoconstriction, a condition for which bronchodilation would be indicated. Nevertheless, this author does not routinely use bronchodilators in feline HWD.

The use of aspirin has been questioned because vascular changes associated with HW1 consume platelets, increasing their turnover rate and effectually diminishing the antithrom-botic effects of the drug. Conventional doses of aspirin did not prevent angiographically detected vascular lesions. Doses of aspirin necessary to produce even limited histologic benefit approached the toxic range. Despite this, because therapeutic options are limited, at conventional doses (80 mg orally, every 72 hours), aspirin is generally harmless, inexpensive, and convenient. Because the quoted studies were based on relatively insensitive estimates of platelet function and pulmonary arterial disease (thereby possibly missing subtle benefits), the author continues to advocate aspirin for cats with HWI. Aspirin is not prescribed with concurrent corticosteroid therapy. Management of other signs of heartworm disease in cats is largely symptomatic.


Canine Heartworm Disease: Ancillary Therapy


The anti-inflammatory and immunosuppressive effects inherent to corticosteroids are useful for treatment of some aspects of HWD. Prednisone, the steroid most often advocated, reduces pulmonary arteritis but actually worsens the proliferative vascular lesions of HWD, diminishes pulmonary arterial flow, and reduces the effectiveness of thiacetarsemide. For these reasons, corticosteroids are indicated in heartworm disease only in the face of pulmonary parenchymal complications (eosinophilic pneumonitis, eosinophilic granulomas, and PTE), to treat or prevent adverse reactions to microfilaricides, and possibly to minimize tissue reaction to melarsomine. For allergic pneumonias, prednisone (1 mg/kg/day) is administered for 3 to 5 days and discontinued or tapered as indicated. The response is generally favorable. Prednisone has also been advocated, along with cage rest, for the management of postadulticidal thromboembolization at 1 to 2 mg/kg per day, continued until radiographic and clinical improvement is noted. Because of the potential for steroid-induced fluid retention, such therapy should be used cautiously in the face of heart failure. In addition, caution is warranted because early studies demonstrated that postadulticidal corticosteroid therapy reduced pulmonary blood flow and worsened intimal disease in a model of HWI; corticosteroids are also procoagulant As mentioned with adulucidal (previously discussed) and microfilaricidal (discussed following) therapies, corticosteroids may be used to minimize potential adverse reactions to melarsomine and to macrolides given to rapidly kill microfilariae.


Antithrombotic agents have received a good deal of attention in the management of HWD. Potential benefits include reduction in severity of vascular lesions, reduction in thromboxane-induced pulmonary arterial vasoconstriction and PHT, and minimization of postadulticidal PTE. Aspirin has shown success in diminishing the vascular damage caused by segments of dead worms, reduced the extent and severity of myointimal proliferation caused by implanted living worms, and improved pulmonary parenchymal disease and intimal proliferation in dogs receiving thiacetarsemide after previous living heartworm implantation. More recent studies, however, have produced controversial results. Four dogs with implanted heartworms, receiving adulticide and administered aspirin, showed no improvement in pulmonary angio-graphic lesions, and treated dogs had more severe tortuousity than did controls and dogs receiving heparin. Boudreau and colleagues demonstrated that the aspirin dose required to decrease platelet reactivity by at least 50% was increased by nearly 70% with heartworm infection (implantation model) and by nearly 200% with a model (dead worm implantation) of PTE. There were not significant differences in severity of pulmonary vascular lesions in aspirin-treated versus control dogs. For these reasons, the American Heartworm Society does not endorse antithrombotic therapy for routine treatment of HWD. Calvert and colleagues have, however, successfully used the combination of aspirin and strict cage confinement with adul-ticidal therapy for severe HWD.

If used, aspirin is administered daily beginning 1 to 3 weeks prior to and continued for 4 to 6 weeks after adulticide administration. With protracted aspirin therapy, packed cell volume (PCV) and serum total protein, should be monitored periodically. Aspirin is avoided or discontinued in the face of gastrointestinal (GI) bleeding (melena or falling PCV), persistent emesis, thrombocytopenia (50,000/mm), and hemoptysis.

Heparin Therapy

Low-dose calcium heparin has been studied in canine heartworm disease and shown to reduce the adverse reactions associated with thiacetarsemide in dogs with severe clinical signs, including heart failure. In this study, calcium heparin administered at 50 to 100 IU/kg subcutaneously every 8 to 12 hours for 1 to 2 weeks before and 3 to 6 weeks after adulticidal therapy, reduced thromboembolic complications and improved survival, as compared with aspirin and indobufen. Dogs in both groups also received prednisone at 1 mg/kg/day. It is emphasized that this therapy has not been studied with melarsomine adulticidal therapy. Calvert and colleagues advocate sodium heparin (50 to 70 U/kg) in dogs with thrombocytopenia, DIC, or both, continuing until the platelet count is greater than 150,000/mm, for at least 7 days, and possibly for weeks.

Microfilaricidal Therapy

Despite the fact that no agent is approved by the Food and Drug Administration for the elimination of microfilaria, microfilaricidal therapy is traditionally instituted 4 to 6 weeks after adulticide administration. The macrolides offer a safe and effective alternative to levamisole and dithiazanine. Microfilariae are rapidly cleared with ivermectin at 50 ug/kg (approximately eight times preventative dose) or milbemycin at 500 mg/kg (preventative dose), although this represents an extra-label use of ivermectin. Adverse reactions, the severity of which is likely related to microfilarial numbers, were observed in 6% of 126 dogs receiving ivermectin at the microfilaricidal dose. Signs included shock, depression, hypothermia, and vomiting. With fluid and corticosteroid (dexamethasone at 2 to 4 mg/kg intravenously) therapy, all dogs recovered within 12 hours. One fatality, however, was observed 4 days after microfilaricidal therapy. Similar findings and frequency have been reported with milbemycin at the preventative dose. Dogs so treated should be hospitalized and carefully observed for the day. Dogs less than 16 kg, harboring more than 10,000 microfilaria per milliliter of blood, are more apt to suffer adverse reactions. Benadryl (2 mg/kg intramuscularly) and dexamethasone (0.25 mg/kg intravenously) can be administered prophylactically to prevent adverse reactions to microfilaricidal doses of macrolides.

A slower microfilarial kill rate can also be achieved with ivermectin, moxidectin, and selamectin at preventative doses. Using either the rapid or “slow kill” approach rids the patient of microfilariae and sterilizes the female heartworm.

The American Heartworm Society recommends that macrolide therapy, at preventative doses, be instituted 3 to 4 weeks after adulticidal therapy. Accelerated microfilaria] destruction can be achieved using recommended doses of milbemycin or by reducing the dosing interval for the other topical or oral formulations to every 2 weeks. Filter or modified Knott tests are rechecked in 5 months when using a slow kill or after 2 to 3 macrolide doses when using a accelerated dose. This interval for testing can be reduced if milbemycin or high-dose ivermectin (50 ug/kg) is chosen.

This author chooses an alternative approach (), beginning the administration of a macrolide preventative at the time of diagnosis, often days to weeks prior to adulticidal therapy. With the slow kill microfilaricides (ivermectin, moxidectin, or selamectin at preventative doses), little chance exists of an adverse reaction; however, the owner is warned of the possibility and advised to administer the medication on a day when he or she will be at home. If milbemycin is used, it is usually administered in the hospital and may be preceded by administration of dexamethasone and Benadryl (as described previously in adulticidal therapy).