Veterinary Medicine

Balanced vasodilators

Sodium nitroprusside

Sodium nitroprusside is a potent arteriolar and venodilator drug with a similar mechanism of action to the organic nitrates, h has a very short duration of action and is administered by continuous intravenous infusion starting at an initial infusion rate of 1-5 μg kg-1 min-1. It reduces pulmonary and systemic vascular resistance decreasing ventricular filling pressure and is most useful in the management of acute, life-threatening cardiogenic pulmonary oedema. The dose can be titrated upwards to effect whilst monitoring arterial blood pressure since excessive falls in arterial blood pressure are an indication of overdosage. The effects are reversed within 1-10 min of slowing the infusion rate allowing fine control of the drug’s effects. Since delivery of the drug requires accurate control at a low rate of fluid administration, an infusion pump should be used. In dogs with severe cardiac failure resulting from poor systolic function (dilated cardiomyopathy), a drug providing positive inotropic support (for example dobutamine) is required in addition to sodium nitroprusside, otherwise the reduction in preload caused by venodilation may result in a precipitous fall in cardiac output. Intravenous infusion of sodium nitroprusside should not exceed 48 h since toxic metabolites (thiocyanate) build up in the circulation. Infusions should be stopped gradually rather than abruptly to prevent rebound increases in vascular resistance and cardiac filling pressures.


Prazosin is a balanced vasodilator drug which can be given orally to dogs. It is an alpha1-selective adrenoceptor antagonist which blocks excessive sympathetic stimulation of vascular alpha1-adrenoceptors without affecting the autoinhibition of noradrenaline release by presynaptic alpha2-adrenoceptors. The recommended dosage is 1 mg tid for dogs weighing less than 15 kg and 2 mg tid for dogs weighing more than 15 kg. In humans and experimental animals, although prazosin is very effective initially, with repeated dosing its effects become attenuated, possibly as the renin-angiotensin system assumes greater importance in regulating vascular tone.

Angiotensin converting enzyme inhibitors

Given the effects of angiotensin II which are central to the pathophvsiology of chronic heart failure, the effects of drugs which inhibit the formation of angiotensin II by inhibition of anglotensin converting enzyme (ACE) are predictable. They are balanced vasodilators and will enhance the excretion of sodium and water by reducing circulating levels of aldosterone and ADH; thus they have a potassium-sparing diuretic effect. Angiotensin converting enzyme is also responsible for the breakdown of the natural vasodilator, bradykinin and some of the effects of ACE inhibitors can be attributed to potentiating bradykinin. Their effects on the vasculature are less profound and slower to take effect when compared to hydralazine and nitroprusside, hence these drugs are preferred to the ACE inhibitors when dealing with cases of life-threatening pulmonary oedema due to left-sided heart failure. Indeed, clinical signs may continue to improve for several weeks in human heart failure patients on ACE inhibitors and multicentre controlled clinical trials in veterinary medicine suggest that the same is true in veterinary medicine. Small but significant effects have been demonstrated on survival time of dogs with dilated cardiomyopathy and mitral valvular heart disease treated with enalapril.

Captopril was the first ACE inhibitor to be produced. It contains a sulphydryl group which causes certain side effects which are common to sulphydryl compounds, namely alterations in taste perception, proteinuria and drug-induced blood dyscrasias. The recommended dosage is 0.5-2.0 mg kgr-1 three times daily. Oral absorption is reduced by food. Exceeding the upper limit of this dose gives no further beneficial therapeutic effect but increases the drug’s toxiciry. Angiotensin II may maintain glomerular filtration pressures in the face of poor renal perfusion by constricting the efferent arteriole more than the afferent arteriole. Removal of this protective mechanism may precipitate acute renal failure in some patients with subclinical, pre-existing renal dysfunction. Hence blood plasma urea and creatinine should be determined in animals before and after they are put on ACE inhibitors. As with other vasodilator drugs, hypotension is a possible side effect, particularly if used in combination with high doses of diuretics. In humans. ACE inhibition has been associated with a drug-induced cough.

Enalapril is an ACE inhibitor with significant advantages over captopril. It does not possess a sulphydryl group and so lacks the associated side effects mentioned above. It is a pro-drug, the active form being a metabolite, enalaprilat, formed by the liver. The onset of action is slower than captopril and its duration of effect is longer (12-14 h). Recommended dosing in dogs is 0,5-1.0 mg kg-1 every 12-24 h and in cats is 0,25 mg kg-1 every 12 h. Side effects are those associated with ACE inhibition described above for captopril.

Benazepril is an ACE inhibitor recently licensed for veterinary use. It shares many properties with enalapril, lacking a sulphydryl group and being a pro-drug. In addition, the excretion of the active metabolite from the body occurs both in the bile and the urine. This contrasts with enalapril, which is eliminated in the urine only where dose adjustment may be necessary in animals with significant impairment of renal function. The recommended dose rate of benazepril for the dog is 0.25 to 0.5 mg kg-1 orally every 24 hours. Currently, there is no authorized dose rate for cats.

Veterinary Procedures

Blood Pressure Measurement: Indirect

Patient Preparation

None required.


Generally, two techniques are used. Oscillometric blood pressure (BP) measurement entails use of an automated recording system. A cuff is applied to the base of the tail or a distal limb for access to an artery. This technique generally is regarded as being most accurate in dogs. When oscillometric BP measurements are performed in dogs, the patient should be in lateral recumbency. This places the cuff at approximately the same level as the heart. In cats the patient generally remains in sternal recumbency (and minimally restrained). Most patients experience a brief acclimation period to the cuff placement. For this reason, at least three to five separate readings are obtained at 1- to 2-minute intervals. This technique can be used on awake or anesthetized patients ().

The Doppler-ultrasonic flow detection system is most accurate in cats for measuring systolic BP. Again, the ventral tail base or a dorsal pedal artery (hindlimb) or the superficial palmar arterial arch (forelimb) can be used. Apply and inflate an occluding cuff. The readings are obtained by a transducer as the pressure on the cuff is reduced. Caution is recommended in interpreting results from dogs that are reported as hypertensive but have no overt clinical disease. The higher reported occurrence of falsely elevated BP in normotensive dogs measured by this method justifies additional scrutiny when interpreting Doppler BP results in dogs.

TABLE Systolic Blood Pressure

  Normal Hypertension Hypotension  
Dog and cat 100-150 mm Hg > 160 mm Hg

>180mmHg(high risk)


Clinically, the most common use of indirect BP measurement is in assessing cats for the presence (or absence) of systemic hypertension caused by renal insufficiency or hyperthyroidism (thyrotoxicosis). A common finding among untreated hypertensive cats is retinal detachment and blindness. Early detection and therapeutic intervention (e.g., enalapril and or amlodipine) is critical. In dogs, BP measurement is indicated in patients with chronic renal insufficiency and/or protein-losing nephropathy, hyperadrenocorticism, and diabetes mellitus. In veterinary medicine, interpretation of BP centers on the systolic BP reading, not the diastolic reading (Table Systolic Blood Pressure).


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.


HCM: Pathophysiology

Hypertrophy, Diastolic Dysfunction, and Congestive Heart Failure

Enlarged papillary muscles and a thick left ventricular myocardium with a normal to small left ventricular chamber characterize hypertrophic cardiomyopathy. hypertrophic cardiomyopathy may be mild, moderate, or severe. Severe concentric hypertrophy by itself increases chamber stiffness. In addition, blood flow and especially blood flow reserve to severely thickened myocardium is compromised, which causes myocardial ischemia, cell death, and replacement fibrosis. This has been documented in cats by showing that cardiac troponin I concentration, a protein released into the systemic circulation after cell necrosis, is increased in cats with severe hypertrophic cardiomyopathy. Increased concentrations of circulating neurohormones may also stimulate interstitial fibrosis. Fibrosis increases chamber stiffness (increased pressure for any given volume) further and is probably the primary reason for the marked diastolic dysfunction seen in this disease. The stiff ventricular chamber causes a greater increase in pressure for any given increase in volume when the ventricle fills in diastole. This produces congestive heart failure (i.e., pulmonary edema and pleural effusion).The myocardium from cats with hypertrophic cardiomyopathy also takes a longer time to relax in early diastole, although the clinical significance of this is unknown. When left ventricular hypertrophy is severe, it is common for the left ventricular wall thickness to be twice the normal thickness. Consequently, left ventricular wall thickness is commonly in the 7 to 10 mm range when hypertrophic cardiomyopathy is severe in cats. This severe concentric hypertrophy may encroach on the left ventricular cavity in diastole, decreasing its size, although left ventricular diastolic diameter is commonly within the normal range. The end-systolic volume and diameter are almost always reduced, often to zero (endsystolic cavity obliteration). Global myocardial contractility is normal in humans with hypertrophic cardiomyopathy, and die reduction in end-systolic volume is due to a decrease in afterload (wall stress) brought on by the increase in wall thickness.

Systolic Anterior Motion of the Mitral Valve A phenomenon called systolic anterior motion (SAM) of the mitral valve is common in cats with hypertrophic cardiomyopathy ().

Cats with hypertrophic cardiomyopathy and systolic anterior motion are commonly said to have the obstructive type of hypertrophic cardiomyopathy or hypertrophic obstructive cardiomyopathy (HOCM). In one survey of 46 cats, systolic anterior motion was present in 67%. systolic anterior motion of the mitral valve is the process of the septal (anterior] mitral valve leaflet or the chordal structures inserting on this leaflet being pulled into the left ventricular outflow tract during systole. Here it is caught in the blood flow and pushed toward (and often ultimately against) the IVS. The initial pulling of the mitral valve leaflet toward the left ventricular outflow tract in systole can clearly be seen on many echocardiograms from cats with hypertrophic cardiomyopathy. The grossly enlarged papillary muscles encroach on the left ventricular outflow tract (the region of the left ventricular between the anterior leaflet of the mitral valve and the IVS in diastole) and pull the mitral apparatus structures into the basilar region of the outflow tract. This situation has been reproduced experimentally in dogs by surgically displacing the papillary muscles cranially. systolic anterior motion of the mitral valve produces a dynamic subaor-tic stenosis that increases systolic intraventricular pressure in mid- to late systole. The dynamic subaortic stenosis increases the velocity of blood flow through the subaortic region and often produces turbulence. Simultaneously, when the septal leaflet is pulled toward the IVS, this produces a gap in the mitral valve, creating mitral regurgitation. These abnormalities are by far the most common cause of the heart murmur heard in cats with hypertrophic cardiomyopathy. The process of systolic anterior motion is dynamic — worsening when contractility increases and lessening when contractility decreases. This also makes the murmur dynamic — increasing in intensity with increasing excitement and softening when the cat becomes calmer.

Pleural Effusion Along with pulmonary edema, pleural effusion is common in cats with heart failure. It can be a modified transudate, pseudochylous or true chylous in nature. The most common cause of chylothorax in cats is heart failure. It is unknown exactly why pleural effusion develops in these cats. Two possibilities exist: The first is that left heart failure results in pulmonary hypertension severe enough to cause right heart failure. This does not appear to occur very frequently in cats because it is unusual to identify echocardiographic right heart enlargement, jugular and hepatic vein distension, or ascites in these cases. The second possibility is that feline visceral pleural veins drain into the pulmonary veins such that elevated pulmonary vein pressure (congestive left heart failure) causes the formation of pleural effusion. In the dog the visceral pleura is supplied by pulmonary arteries and drained by pulmonary veins. The dog, the cat, and the monkey have type II lungs.w One characteristic of type II lungs is that the visceral pleura is supplied not by bronchial arteries but by pulmonary arteries.

Presumably this means that the cat visceral pleura is also drained by pulmonary veins. This means that pulmonary venous hypertension secondary to left heart failure could cause pleural effusion in cats as it does in humans.

Pathology of hypertrophic cardiomyopathy

Gross Pathology Cats with severe hypertrophic cardiomyopathy have severe thickening of the left ventricular myocardium (the IVS and free wall), with the left ventricular wall commonly being 7 to 10 mm thick (). The hypertrophy may be symmetrical, involving the entire circumference of the LV, but it may also be asymmetrical. In some cats the IVS is significandy thicker than the free wall, whereas in others the free wall is thicker (asymmetrical hypertrophy). In those cats with primarily septa] hypertrophy, the hypertrophy may be confined to the basilar region of the septum, and in others may be apical. Isolated free wall hypertrophy most commonly occurs in the region between the papillary muscles. As in many pathologic specimens, hearts from cats with hypertrophic cardiomyopathy may undergo contraction (rigor) after death, resulting in a wall thickness that is closer to the end-systolic wall thickness in life rather than the end-diastolic thickness. Consequently, heart weight must be combined with subjective or objective evidence of left ventricular wall thickening to make the diagnosis of hypertrophic cardiomyopathy postmortem. To weigh a cat heart the pericardium should be removed and the aorta and pulmonary artery transected so that no more than 2 to 4 cm are left. Normal heart weight-to-body weight ratio has been reported to be 10.6 +/- 4 g/lb, with cats with hypertrophic cardiomyopathy having a ratio of 13.2 +/-3.1 g/1b. This results in a large overlap between the two groups. In the author’s experience, most normal-sized cats (6 to 12 lb) have a heart that weighs less than 20 g and most cats in this size range with hypertrophic cardiomyopathy have a heart that weighs more than 20 g. Cats with severe hypertrophic cardiomyopathy almost always have a heart that weighs more than 25 g, usually over 30 g, and can be as heavy as 38 g.

The left atrium is often enlarged in cats with severe hypertrophic cardiomyopathy, often markedly so. However, with early, severe disease, the author has identified normal left atrial size in some Maine coon cats. Occasionally a thrombus is present in the body of the left atrium or within the left auricle.

Cats with milder forms of the disease (mild to moderate hypertrophic cardiomyopathy) have lesser wall thickening and a more normal-sized left ventricular chamber. The left atrium may be normal in size or may be enlarged. Papillary muscle hypertrophy may be the predominant lesion.

Histopathology Histopathologically, a wide range of abnormalities exist. In some hearts, only myocyte hypertrophy is evident. On the other end of the spectrum, some cats have moderate to severe interstitial and replacement fibrosis and dystrophic mineralization (20% to 40% of cases). Intramural coronary arteriosclerosis is present in approximately 75% of cats with hypertrophic cardiomyopathy. Intramyocardial small artery disease is not specific for hypertrophic cardiomyopathy because it is also identified in cats and dogs with many cardiac diseases.

In humans, myocardial fiber disarray that involves at least 5% of the myocardium in the IVS is found in 90% of patients with familial hypertrophic cardiomyopathy. Other diseases that produce concentric hypertrophy can also cause myocardial fiber disarray, but this almost always involves less than 1% of the myocardium. In cats with hypertrophic cardiomyopathy, myocardial fiber disarray in the IVS of the same magnitude observed in humans is only identified in 30% to 60% of cases.’ However, myocardial fiber disarray is a consistent feature of hypertrophic cardiomyopathy in Maine coon cats. Sarcomeres also have disarray in human patients with hypertrophic cardiomyopathy. Interestingly, infecting isolated feline cardiocytes with an adenoviral vector containing a full-length mutated human β-myosin heavy chain gene causes sarcomere disruption.

Natural History and Prognosis

The prognosis, as with most cardiac diseases, is highly variable for hypertrophic cardiomyopathy. Some of it is determined by clinical presentation and echocardiographic severity of the disease. Adult cats that are asymptomatic and have mild to moderate disease and no to mild left atrial enlargement have a good short-term (and possibly a good long-term) prognosis. Some, however, may progress to more severe disease and some may die suddenly. Asymptomatic cats with severe wall thickening and mild to moderate left atrial enlargement have a guarded prognosis for developing heart failure in the future. They probably have some risk for developing thromboembolism and may be at risk for sudden death. Cats with no clinical signs but with severe wall thickening and moderate to severe left atrial enlargement are at risk for developing heart failure or often already have mild to moderate heart failure that has gone undetected. These cats are at risk for developing systemic thromboembolic disease and sudden death, although both of these risks appear to be relatively small. Cats presented in heart failure usually have a poor prognosis, but survival time is highly variable. Most die of intractable heart failure. Some develop thromboembolism, and some die suddenly. In one study a MST of 3 months was reported yet some cats (about 20% in one study) in this class stabilize and do well for prolonged periods. The author and colleagues have seen some cats with severe hypertrophic cardiomyopathy live as long as 2.5 years after the diagnosis of heart failure. Some of these cats may develop heart failure when they are stressed and become severely tachycardic and then stabilize after that time. Cats with severe hypertrophic cardiomyopathy and aortic thromboembolism in the aforementioned study had a very poor prognosis with a MST of 2 months.

Hypertrophic Cardiomyopathy: Clinical Manifestations

Differential Diagnoses

Hyperthyroidism and systemic hypertension need to be ruled out as either primary or complicating factors. Hyperthyroidism is usually easy to rule out. Devices to measure blood pressure in the cat, however, are not always readily available, and the technique requires some practice to acquire accurate values. In addition, systolic systemic arterial blood pressure may be increased in a normal cat that is stressed, so repeat measurements of increased blood pressure are preferred before a diagnosis of systemic hypertension is made If systemic arterial blood pressure cannot be measured, one should at least rule out the common causes of systemic hypertension in a cat with left ventricular concentric hypertrophy (i.e., hyperthyroidism, renal failure).

Rarely, infiltrative disease such as lymphoma will produce hypertrophy that is indistinguishable from hypertrophic cardiomyopathy on an echocar-diogram. One such case has been reported. Cats that are homozygous for the dystrophin deficiency seen in hypertrophic feline muscular dystrophy also have thickened but hypoechoic myocardium with hyperechoic foci in the left ventricular myocardium and papillary muscles. The myocardium contains foci of mineralization and no dystrophin.

Precipitating Factors

Certain factors may precipitate heart failure or sudden death in a cat with hypertrophic cardiomyopathy. Stress (cat fight), anesthesia (especially with ketamine), and surgery appear to be factors. The administration of a long-acting corticosteroid also appears to be a factor that either produces or worsens heart failure in cats, presumably through the mineralocorticoid effects of these drugs.

Therapy of Cats with No Clinical Signs

No evidence exists to show that any drug alters the natural history of hypertrophic cardiomyopathy in domestic cats until they are in heart failure. Diltiazem, atenolol, or enalapril are commonly administered to cats with mild to severe hypertrophic cardiomyopathy that are not in heart failure on an empiric basis. Whenever hypertrophic cardiomyopathy is diagnosed in a cat, the veterinarian should explain the situation to owners and try to let them make informed decisions based on their wishes and life styles. Because no intervention is known to change the course of the disease, treatment at this stage is not mandated.

Treatment Goals and General Therapy of Cats in Heart Failure

Cats that present in heart failure have clinical signs referable to pulmonary edema, pleural effusion, or both. Consequendy, therapy is generally aimed at decreasing left atrial and pulmonary venous pressures in these cats and physically removing the effusion. In some cats with severe heart failure, clinical evidence of hypoperfusion (low-output heart failure) may be apparent in addition to the signs of congestive heart failure. The signs may be manifested primarily as cold extremities.

Pulmonary edema is primarily treated with diuretics (almost exclusively with furosemide) acutely and chronically and an angiotensin-converting enzyme enzyme inhibitor chronically, although recent evidence suggests that angiotensin-converting enzyme inhibition may not be that helpful in prolonging survival in cats with hypertrophic cardiomyopathy. Diltiazem and beta-adrenergic blockers, usually atenolol, have been commonly used as adjunctive agents. Recent evidence suggests that diltiazem is not helpful in prolonging survival in cats with heart failure due to severe hypertrophic cardiomyopathy and that atenolol may actually shorten survival time. Plcurocentesis is most effective for treating cats with severe pleural effusion. Furosemide is helpful for preventing or slowing recurrent effusion.

Hypertrophic Cardiomyopathy: Acute Therapy

Hypertrophic Cardiomyopathy: Chronic Therapy

Refractory Heart Failure

Heart failure that is refractory to furosemide and an angiotensin-converting enzyme inhibitor portends a poor prognosis. Another diuretic may be added to the therapeutic regimen. A thiazide diuretic is generally the mast rewarding but is also more likely to cause complications, such as dehydration and electrolyte (sodium, potassium, chloride, magnesium) depletion. Spironolactone, in theory, may have some beneficial effects related to blocking aldos-terone’s actions; however, clinically it rarely results in noticeable improvement, and its efficacy is unproven. A low sodium diet may be helpful, if palatable. This diet can be a commercial one or one that is devised by a nutritional service. Home-cooked diets formulated by the owner are discouraged unless the owner is counseled. If severe systolic anterior motion is present and atenolol is not already part of the therapeutic regimen, it may be added at this stage.


Hypertrophic Cardiomyopathy: Chronic Therapy

Many aspects of chronic therapy of hypertrophic cardiomyopathy are controversial. All therapy is palliative. Furosemide is the only drug that has a clearly beneficial effect chronically on survival in cats with hypertrophic cardiomyopathy.


Many cats with hypertrophic cardiomyopathy are dyspneic because of pleural effusion that reaccumulates despite appropriate medical therapy. These cats need periodic pleurocentesis ().


In cats with congestive heart failure due to hypertrophic cardiomyopathy, rurosemide administration, once initiated, should usually be maintained for the rest of the cat’s life. In a few cases, furosemide can be discontinued gradually once the cat has been stabilized. This usually only occurs in a cat that has had a precipitating stressful event.

As for dilated cardiomyopathy, the maintenance dose of furosemide in cats usually ranges from 6.25 (one half of a 12.5 mg tablet) once a day to 12.5 mg orally every 8 hours, although the dose may be increased further if the cat is not responding to a conventional dose. The author and colleagues have administered higher doses (up to 37.5 mg every 12 hours) than commonly recommended to a few cats with severe heart failure without identifying severe consequences as long as the cats were eating and drinking. Cats on high-dose furosemide therapy are commonly mildly dehydrated and mildly to moderately azotemic. However, they often continue to maintain a reasonable quality of life.

The furosemide dose needs to be titrated carefully in each patient. The owner should be taught how to count the resting respiratory rate at home and instructed to keep a daily written log of the respiratory rate as oudined previously under dilated cardiomyopathy. This is highly beneficial for making decisions regarding dose adjustment in individual patients.

Angiolensin-Converting Enzyme Inhibitors

Although furosemide has been used to treat heart fadure secondary to feline hypertrophic cardiomyopathy for decades, the use of angiotensin-converting enzyme inhibitors in cats with hypertrophic cardiomyopathy is relatively recent, because veterinarians, like their colleagues who treat humans, feared that the use of angiotensin-converting enzyme inhibitors would worsen systolic anterior motion in their patients. Over the past 10 years it has become obvious to most veterinary cardiologists that angiotensin-converting enzyme inhibitors do not worsen the clinical signs referable to hypertrophic cardiomyopathy, and a recent study has documented that systolic anterior motion is not worsened by enalapril administration in cats. Many have believed and one study has suggested that angiotensin-converting enzyme inhibitors improve the quality and quantity of life of cats with hypertrophic cardiomyopathy. Preliminary evidence from a recent placebo-controlled and blinded clinical trial suggests that enalapril produces little to no benefit when compared with furosemide alone in cats with heart failure due to hypertrophic cardiomyopathy. However, this study also included cats with unclassified (restrictive) cardiomyopathy and both cats with and without SAM. Subgroup analysis failed to change the conclusions of the study but die subgroups were small. Consequendy, it is the recommendation of this author to continue to use an angiotensin-converting enzyme inhibitor in cats in heart failure due to hypertrophic cardiomyopathy at a dose of 1.25 to 2.5 mg orally every 24 hours.


In cats with severe hypertrophic cardiomyopathy that have or have had evidence of CHF, diltiazem or a beta-adrenergic blocking agent are often administered. Both provide symptomatic benefit in human patients. Their use in cats with hypertrophic cardiomyopathy is controversial; however, little doubt exists that neither drugs produces dramatic benefits. Diltiazem, however, appears to produce no harm.M

Diltiazem is a calcium channel blocker previously reported to produce beneficial effects in cats with hypertrophic cardiomyopathy when dosed at 7.5 mg every 8 hours. Beneficial effects that have been reported include lessened edema formation and decreased wall thickness in some cats. In the author’s experience only a few cats appear to experience a clinically significant decrease in wall thickness, and it is impossible to tell ii this is due to drug effect or time. Rarely does it appear clinically that diltiazem controls congestive heart failure on its own or helps control pulmonary edema or pleural effusion when added on to furosemide therapy. Diltiazem does improve the early diastolic relaxation abnormalities seen in feline hypertrophic cardiomyopathy. Whether this helps decrease diastolic intraventricular pressure and so decrease edema formation is unknown. Theoretically it should have little benefit in the resting cat with a slow heart rate. Slower myocardial relaxation during rapid heart rates may not allow the myocardium enough time to relax, resulting in increased diastolic intraventricular pressure. Diltiazem may help protect a cat that undergoes a stressful event. Incomplete relaxation and decreased compliance, however, are more plausible explanations for increased diastolic pressure due to diastolic dysfunction in feline hypertrophic cardiomyopathy. In humans, diltiazem does not change left ventricular chamber stiffness and so does not alter passive diastolic function. In cats it also appears not to alter late diastolic filling properties. Diltiazem decreases SAM, which may decrease the amount of mitral regurgitation, but beta blockers generally produce a greater decrease in the amount of SAM. Recent evidence suggests that diltiazem has no effect on survival time in cats with severe hypertrophic cardiomyopathy and heart failure.

Dilacor XR is dosed at 30 mg per cat orally every 12 hours and produces a significant decrease in heart rate and blood pressure in cats with hypertrophic cardiomyopathy for 12 to 14 hours.

Beta-Adrenergic Receptor Blockers

Beta blockers are primarily used to reduce systolic anterior motion and heart rate in cats with hypertrophic cardiomyopathy. At this stage, beta blockers should probably be reserved for cats with severe systolic anterior motion at rest or with tachyarrhythmias and not routinely administered to the affected population as a whole, because a recent study has suggested that atenolol shortens the survival of cats with diastolic dysfunction, including cats with hypertrophic cardiomyopathy. Beta blockade is questionable for systolic anterior motion and tachycardia observed in a clinical situation. Cats spend 85% of their life asleep, and sleep probably reduces sympathetic activity better than a beta-adrenergic blocking drug. Consequently, many cats with mild to moderate systolic anterior motion in a veterinary clinic probably have no or milder systolic anterior motion at home, and the same can be said for tachycardia. Beta blockers are effective for reducing SAM. Two studies have examined the effects of esmolol, a short-acting Bradrenergic blocking drug, in cats with hypertrophic cardiomyopathy and obstruction to left ventricular outflow due to SAM; both showed a reduction in the pressure gradient across the outflow tract In both studies the degree of outflow tract obstruction decreased and the heart rate slowed, and in one esmolol was more effective than diltiazem. If the data on esmolol can be translated to atenolol’s effects in cats (which seems reasonable), one would predict that atenolol would decrease SAM.

Atenolol is a specific pVadrenergic blocking drug that needs to be administered twice a day, usually at a total dose of 6.25 to 12.5 mg orally every 12 hours. In the cat, atenolol has a half-life of 3.5 hours. When administered to cats at a dose of 1.4 mg/lb, atenolol attenuates the increase in heart rate produced by isoproterenol for 12 but not for 24 hours.


Dilated Cardiomyopathy: Breed Variations

There is an increasing amount of breed specific information about canine dilated cardiomyopathy. Because of differences the specific breed should be considered when considering etiology, developing treatment plans, and providing prognostic information.

Occasionally, atypical breeds of dogs develop dilated cardiomyopathy. The etiology of the disease in these cases is unknown.

Cocker Spaniels

Dilated cardiomyopathy has been reported in both American and English cocker spaniels; however, dilated cardiomyopathy occurs less commonly in this breed than valvular endocardiosis.

An association between the development of dilated cardiomyopathy and low plasma taurine levels has been reported in some American cocker spaniels. Dogs provided taurine and i.carnitine supplementation showed an increase in FS% and a decrease in LVEDD and LVESD over a 4-month period, although myocar-dial function did not return to normal. This study suggests that at least some Cocker spaniels with dilated cardiomyopathy may benefit from supplementation with taurine and, perhaps I.carnitine. The current recommendations for American cocker spaniels with dilated cardiomyopathy are to measure plasma taurine levels (normal >50 µg/ml) and to treat with 500 mg of taurine orally every 12 hours and 1.0 gram of l.camitine orally every 12 hours. Additional treatment should be given as needed to address such conditions as congestive heart failure and arrhythmias. The investigators suggest that supportive cardiovascular medications can be gradually withdrawn after the FS% increases to more than 20% (usually 3 to 4 months of supplementation). Supplementation with taurine, and L-camitine if possible, should be continued for life. If taurine deficiency is not identified the prognosis is poorer.

English cocker spaniels also get a form of dilated cardiomyopathy but a relationship to taurine or camitine levels has not been well studied. Many reported dogs were from the same kennel, which may suggest a heritable component. Profound evidence of left ventricular enlargement on the electrocardiogram with R wave amplitudes more than 3.0 mV in lead II was frequently observed. Some of the reported dogs died suddenly, but many have had a prolonged, fairly asymptomatic course of disease, or a long survival (years) with medical management.


Male dogs appear to be over represented in Dalmatian dilated cardiomyopathy, although large studies have not been performed. All dogs had adult onset disease and presented for signs consistent with left heart failure (cough, dyspnea) or syncope. None of the dogs had evidence of biventricular heart failure. Electrocardiography frequendy demonstrated sinus rhythm or sinus tachycardia with occasional ventricular ectopy. Atrial fibrillation was not observed in any of the dogs. Duration of survival ranged from 1.5 to 30 months with euthanasia due to refractory congestive heart failure. None of the dogs died suddenly. Interestingly, the majority (8/9) of reported dogs had been fed a low protein diet for all or part of their lives for prevention or treatment of urate stones. The cause and effect of these diets on the development of dilated cardiomyopathy is not known, but Dalmatians that develop dilated cardiomyopathy that are being fed a low protein diet should be switched to a more balanced diet if possible.

Occasionally Dalmatians develop acquired AV valve disease, so this should be considered as an important differential diagnosis.

Dobermcin Pinschers

The Doberman pinscher is one of the most commonly reported breeds of dogs to be affected with dilated cardiomyopathy in North America. It is characterized as an adult disease that results in the development of left and/or biventricular failure, often with atrial fibrillation. However, about 30% of the dogs develop ventricular tachyarrhythmias and may present for syncope or die of sudden death before the development of heart failure, and in some cases, before the development of ventricular dilation and systolic dysfunction.

Dilated cardiomyopathy in this breed is believed to be familial, although the pattern of inheritance is not well documented.

The clinical stage of dilated cardiomyopathy in the Doberman pinscher appears to be malignant in comparison to the disease in other breeds. The median survival time for dogs once heart failure has developed is 9.6 weeks. Atrial fibrillation and bilateral congestive heart failure are poor prognostic signs. However, the occult stage appears to be slowly progressive (2 to 3 years), and some affected dogs die from noncardiac disease before they become symptomatic from dilated cardiomyopathy. Although there is only a small amount of evidence, there may be some benefit to early diagnosis and initiation of treatment in the occult stage (as discussed below).

Some Doberman pinschers develop syncope or die suddenly before left ventricular dilation or systolic dysfunction ever develops. In most cases, these symptoms are associated with the presence of ventricular tachyarrhythmias. However, bradycardia-associated episodic weakness and syncope has also been observed in cardiomyopathic Doberman pinschers. Therefore Holter monitoring should be performed on the syncopal dog to document the causative arrhythmia before treatment is initiated.

The timing and procedure for treatment of ventricular arrhythmias in the affected dog is not clear cut. Rapid ventricular tachycardia, complex ventricular arrhythmias, or the combination of ventricular arrhythmias, ventricular dilation, and systolic dysfunction is thought to be associated with a higher risk of sudden cardiac death and to be indications for treatment, but this has not been well documented. Additionally, some dogs die suddenly without having any of these arrhythmias documented. If treatment is warranted, consideration might be given to the use of one of several ventricular antiar-rhythmics. Sotalol, a combination beta-blocker and potassium channel Mocker, may be beneficial in some cases but should be used with caution if systolic dysfunction is present. Amiodarone has been studied in the affected Doberman pinscher at a dose of 10.0 mg/kg orally every 12 hours for 1 week, followed by 8.0 mg/kg every 24 hours. After 6 months the dose may be reduced to 5.0 mg/kg every 24 hours. Careful evaluation of serum concentrations, complete blood counts (neutropenia has been reported), and liver enzymes monthly is suggested. Although the goals of treatment include decreasing the number of VPCs, decreasing symptoms, and decreasing the risk of sudden death. The ability of any antiarrhythmic to reach these goals for these cases has not been proven.

Evidence that the disease is familial and that early intervention may increase survival has lead to significant interest in screening asymptomatic dogs for signs of early disease. Annual echocardiography and ambulatory electrocardiography (Holter monitoring) are believed to be the best predictors of early dilated cardiomyopathy. Criteria that are believed to be indicators of occult disease include an echocardiographically determined LVEDD more than 4.6 cm and a LVESD more than 3.8 cm, even in the absence of systolic dysfunction. These numbers are based on average sized dogs and may not be valid for very large dogs. Annual Holter monitoring has also been recommended to detect Doberman pinschers that may develop ventricular arrhythmias before ventricular dilation and systolic dysfunction. Adult Doberman pinschers with greater than 50 ventricular premature complexes (VPCs) per 24 hours, or with couplets or triplets are suspect for the development of dilated cardiomyopathy,< Owners should be advised that since this is an adult onset disease with variability in the age of onset, screening tests should be performed annually.

Great Danes

Dilated cardiomyopathy in the Great Dane appears to be a familial disease. Affected male dogs were overrepresented, which suggests an X-linked pattern of inheritance in at least some families. If this is true, sons of affected females are at high risk of developing the disease; daughters of affected fathers are likely to be silent carriers.

Affected Great Danes presented most commonly for weight loss and/or coughing. Left-sided heart murmurs, gallops, and ascites were frequently observed. The most common electro-cardiographic findings included atrial fibrillation with occasional ventricular premature complexes. In some cases, atrial fibrillation may develop before any other evidence of underlying myocardial disease (chamber enlargement or systolic dysfunction). These dogs should be carefully followed for the possible development of dilated cardiomyopathy.

Irish Wolfhounds

Atrial fibrillation frequently preceded the development of a heart murmur, clinical signs, and congestive heart failure in the Irish wolfhound with dilated cardiomyopathy and was present in the majority of dogs by the time they developed dilated cardiomyopathy.’ The progression of the disease is not well understood but appears to be slow, with the development of atrial fibrillation preceding the development of congestive heart failure by an average of 24 months. Occasionally, additional electrocardiographic abnormalities have been described, which include ventricular premature complexes and left anterior fas-cicular block patterns. Echocardiography is useful for separation of normal dogs, dogs with occult disease, and dogs with clinical evidence of heart failure. Affected Irish wolfhounds occasionally died suddenly but more commonly were euthanized due to heart failure, most commonly biventricular and sometimes with chylothorax.


Adult-onset dilated cardiomyopathy without a gender predisposition has been reported in the Newfoundland. Clinical presentation included dyspnea, cough, inappetance, and ascites with left or biventricular heart failure. Interestingly a heart murmur was auscultable in a very small percentage of the dogs (4 out of 37). The most common electrical abnormality was atrial fibrillation, but isolated ventricular premature complexes were also observed.

Portuguese Water Dogs

A juvenile form of familial dilated cardiomyopathy has been reported in the Portuguese water dog. Affected puppies were from apparently unaffected parents. Puppies died from congestive heart failure at an average age of 13 weeks after a very rapid course of disease.

Treatment of the Dog with Occult Dilated Cardiomyopathy

Administration of angiotensin converting enzyme (ACE) inhibitors may have some benefit for the dog with early ventricular dilation, with or without systolic dysfunction. Specifically, the use of angiotensin-converting enzyme inhibitors (enalapril, lisinopril, captopril) in the Doberman pinscher with ventricular dilation was found to prolong the amount of time before die onset of CHE Although this study was limited to evaluation of Doberman pinschers, the use of angiotensin-converting enzyme inhibitors for other breeds of dogs with occult dilated cardiomyopathy may be considered. This information provides additional support for the practice of screening adult dogs that are at increased risk of developing dilated cardiomyopathy because of their breed, and perhaps a family history, to allow early medical intervention.

Administration of beta-blockers at this stage is still being evaluated. The addition of low-dose beta-blockers to the treatment of human patients with dilated cardiomyopathy and stable heart failure has demonstrated a reduction in both mortality and morbidity. However, many human patients with dilated cardiomyopathy cannot tolerate even very low doses of beta-blockers and demonstrate rapid cardiac decompensation. The use of beta-blockers for the canine patient with dilated cardiomyopathy has not yet been well studied and a consensus opinion on use of these drugs for patients is not yet available.

Beta-blockers might be considered for the patient with occult disease, but they should be very carefully monitored and should not be given once there is evidence of fluid retention and heart failure until it is very well stabilized. The optimal beta-blocker for this purpose appears to be carvedilol because of its effects on both alpha and beta-receptors. It cannot be overemphasized that the addition of beta-blockers in canine dilated cardiomyopathy patients should be done very cautiously with gradual increases in dosing after a 2-weck period and careful monitoring of heart rate, blood pressure, and symptomology.

Treatment of the Dog with Dilated Cardiomyopathy and CHF

There are no specific therapeutic recommendations for the treatment of dilated cardiomyopathy other than those mentioned above. Nonspecific treatments, including surgery and nutritional supplementation, have been reported but have not yet been shown to have significant long-term benefits for most dogs. As discussed above, early diagnosis and intervention may be of the most benefit. A thorough discussion of treatment of the dog with congestive heart failure is provided elsewhere in this textbook.


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.



Therapy of Heart Failure

Heart failure may be recognized as a clinical end-point in nearly all cardiac diseases. Because the underlying cause of the development of heart failure varies significantly between species and disease conditions, it is often difficult to define heart failure accurately and concisely. In 1994, a panel of the National Heart, Lung and Blood Institute concluded:

Heart failure occurs when an abnormality of cardiac function causes the heart to fail to pump blood at a rate required by the metabolizing tissues or when the heart can do so only with an elevated filling pressure. The heart’s inability to pump a sufficient amount of blood to meet the needs of the body tissues may be due to insufficient or defective cardiac filling and/or impaired contraction and emptying. Compensatory mechanisms increase blood volume and raise cardiac filling pressures, heart rate, and cardiac muscle mass to maintain the heart’s pumping function and cause redistribution of blood flow. Eventually, however, despite these compensatory mechanisms, the ability of the heart to contract and relax declines progressively, and the heart failure worsens.

Because all cardiac diseases have the potential to produce heart failure through similar mechanisms, we frequently view their pathophysiology and therapy from a unified perspective. Agents that promote preload and afterload reduction are used to control the clinical signs associated with elevated filling

Eressures, and neurohormonal modulators are prescribed to lunt the progressive nature of heart disease. This approach allows clinical experience and research to be extrapolated across a wide range of diseases. Although the remainder of this post is written primarily from a unified perspective, caution must be exercised to ensure that the variations within cardiovascular diseases are not forgotten.

Phases Of Heart Failure

Currendy, three distinct phases of heart failure are recognized. Phase 1 constitutes the initial cardiac injury. This phase most frequendy passes silendy, without detectable clinical signs, because compensatory mechanisms (phase 2) are quickly activated. Ultimately, myocardial hypertrophy accounts for the long-term stabilization of cardiac output and the normalization of afterload. Unfortunately, the natural history of cardiac disease often is progressive, and the heart’s ability to hypertrophy is overwhelmed. The previously beneficial short-term compensatory mechanisms now serve only to increase both preload (contributing to the development of congestion) and afterload (increasing myocardial work and oxygen demand). Often a heart murmur, gallop rhythm, cardiac arrhythmia, or cardiomegaly may be identified during this second phase despite the absence of significant or activity-limiting clinical signs. Phase 3 of heart failure is recognized by the emergence of clinical signs (e.g., exercise intolerance, lethargy, coughing, tachypnea) at rest or with minimal activity. Veterinary patients apparendy do not show clinical signs that are recognized by their owners until very late in the disease process. Presumably this may skew our understanding of the natural history of canine and feline cardiovascular disease. This understanding of disease progression is further clouded by the recognition that, depending on the disease process, the first clinical event may be the development of systemic thromboembolism, syncopal episodes, or possibly sudden death.

Natural History Of Cardiovascular Disease

Despite decades of treatment of cardiovascular disease in companion animals, relatively few studies have reported on the survival characteristics of patients afflicted with dilated cardiomyopathy, mitral insufficiency, and hypertrophic cardiomyopathy. The spectrum of clinical signs, therapeutic strategies, breed differences, and disease sequelae hampers the formation of any sweeping conclusions regarding the natural history of these cardiovascular diseases; however, some generalities may be recognized. After dilated cardiomyopathy has been diagnosed, the survival curve drops precipitously for the first 3 months, with median survival times from two retrospective studies reported as 27 days and 65 days. Months 3 through 6 continue to see a large number of dropouts, although interestingly, the curves appear to flatten markedly at approximately 6 months after the initial diagnosis. Whether this represents differences in individual responses to therapy or in the severity of disease at the time of diagnosis is difficult to ascertain.

Analysis of the survival curves for cats with hypertrophic cardiomyopathy presenting with congestive heart failure (CHF) or aortic thromboembolism (ATE) that lived for greater than 24 hours initially showed a steep slope similar to that seen in dogs with dilated cardiomyopathy. Approximately 25% of the congestive heart failure group and 40% of the thromboembolism group died within 3 months of diagnosis. After 3 months, cats presenting for congestive heart failure began to display a less steep, linear survival curve that concluded in a plateau several years after the diagnosis. The survival curve for cats with thromboembolism also displayed some flattening after the first 3 months, although it ukimately remained linear for the rest of the study period. The median survival times were 563 days and 184 days, respectively, for cats with congestive heart failure and those with aortic thromboembolism. Cats with subclinical hypertrophic cardiomyopathy were significantly more likely to die of noncardiac disease (P < 0.001) and displayed a linear mortality curve for the first 4 years, followed by a prolonged plateau for an additional 4 years.

Interestingly, although mitral insufficiency is the most commonly recognized cardiovascular condition in dogs, the natural history and mortality characteristics after the development of congestive heart failure have received little attention. Investigators for the Long-Term Investigation of Veterinary Enalapril (LIVE) study evaluated the time to treatment failure for dogs with congestive heart failure treated with enalapril and standard medical therapy (furosemide with or without digoxin) versus those treated with placebo and standard medical therapy. In the mitral insufficiency subgroup, the number of dogs remaining in the study randomized to placebo mimicked the survival curve of dogs with dilated cardiomyopathy. A relatively high dropout rate was seen over the first 50 days, followed by a prolonged period of stability. The data for dogs randomized to enalapril did not display this steep dropout rate, but rather formed a linear curve from the time of enrollment until completion of the study.

Influences On The Natural History

Unlike in the management of heart disease in humans, veterinary medicine has the profound ability to influence the natural history of cardiovascular disease in companion animals through the use of euthanasia. The ready access to euthanasia in veterinary medicine not only influences patients’ survival times, but also may alter the clinician’s responsibilities in treating the heart failure. A study by Mallery et al. evaluated the factors that contributed to clients’ decision for euthanasia for 38 dogs with congestive heart failure. The most important factors cited were a perceived poor prognosis (37%), recurrent signs of congestive heart failure (26%), and poor quality of life (13%). Common contributing factors included weakness (76%), anorexia (68%), recurrent clinical signs of congestive heart failure (55%), and a poor prognosis (42%). These findings suggest that the goals of the practitioner should include careful client education before and after initiation of medical therapy, along with efforts to improve the patient’s strength, appetite, and quality of life, possibly at the expense of prolonged survival.

Classification Of Heart Failure

Heart Failure: Treatment Strategies

Progression Of Heart Failure

Future Prospects Currently Under Investigation



Progression Of Heart Failure

Traditionally heart failure has been perceived as a hemodynamic disorder that promotes weakness, the development of debilitating congestive signs, deterioration of cardiac function, and ultimately death. Although the initial cardiac insult varies, it was historically rationalized that ventricular remodeling and disease progression occur as consequences of the compensatory mechanisms that promote vasoconstriction and fluid retention. It was recognized that diseased hearts operate on a depressed and flattened Frank-Starling curve, such that volume retention and vasoconstriction, rather than promoting cardiac output, merely exacerbated congestive heart failure. The symptoms of heart failure developed as venous pressures breached the lymphatics’ ability to remove edema or as blood flow to exercising muscles was severely limited.

If disease progression were solely mediated by hemodynamic alterations, it was hypothesized, drugs capable of “unloading” the heart (e.g., vasodilators and positive inotropes) would retard this progression and improve survival. In the first Veterans Affairs Heart Failure Trial (V-HeFT) completed in 1985, prazosin or a combination of hydralazine and isosorbide dinitrate was used to decrease preload and afterload. Although prazosin was more effective at reducing blood pressure, only the hydralazine/isosorbide dinitrate combination reduced mortality compared with placebo. The discordance between the hemodynamic and prognostic findings could not be explained by the traditional perception of heart failure. Support for the hemodynamic hypothesis was further undermined by the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial completed in December of 1994, which found that administration of amlodipine to patients with severe chronic heart failure had no significant effect on mortality.

Similar to the use of vasodilators to decrease ventricular wall stress and increase cardiac output, potent inotropic drugs capable of increasing cyclic adenosine monophosphate levels were developed with the intent to improve survival. If poor pump performance were responsible for the progressive nature of heart failure, it was hypothesized, these positive inotropes should alter the natural course of cardiovascular disease. The phosphodiesterase inhibitor milrinone, which has potent inotropic and vasodilative properties, in fact was found to alter the course of heart failure but in a fashion opposite that expected. In October of 1990, the Prospective Randomized Milrinone Survival Evaluation (PROMISE) trial was stopped 5 months prior to its scheduled completion date because administration of oral milrinone was found to increase all-cause mortality by 28%. Patients with the severest symptoms (i.e., New York Heart Association (NYHA] class IV), who therefore would be the most likely to receive additional medical therapy, showed a 53% increase in mortality. Administration of the partial beta-agonist xamoterol also failed to improve survival in a study of 516 patients.

These drug trial failures were accompanied in the late 1980s and early 1990s by an evolution in the understanding of the traditional hemodynamic model of heart failure. It still was recognized that hemodynamic alterations accounted for the symptomatic manifestations of cardiac disease, but a new understanding of the condition resulted in the conclusion that the body’s compensatory neurohormonal mechanisms contributed to the dilemma of disease progression. Activation of the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS) was found to promote both adverse hemodynamic consequences and direct toxic effects on the myocardium. Cultured mammalian cardiomyocytes exposed to norepinephrine displayed a concentration-dependent decrease in viability that was attenuated significandy by beta-receptor blockade. In addition, norepinephrine was implicated in the provocation of ventricular arrhythmias and the impairment of sodium excretion by the kidneys. Pathophysiologic levels of angiotensin II were found to promote myocytolysis with subsequent fibroblast proliferation, and aldosterone was implicated in the process of myocardial extracellular matrix remodeling. These findings established a connection between hemodynamic mechanisms and neurohormonal consequences, which mutually promote a cycle of disease progression. The initial cardiac insult is followed by activation of neurohormonal compensatory mechanisms that produce further hemodynamic alterations and myocardial fibrosis. Cardiac output continues to decline, the compensatory mechanisms continue to be activated, and the disease process proceeds unabated.

This more complete understanding of the neurohormonal systems led to the development and use of drugs designed to antagonize the RAS. A breakthrough in the management of cardiovascular disease came with the utilization of angiotensin-converting enzyme (ACE) inhibitors in the mid to late 1980’s. Angiotensin-converting enzyme is capable of degrading vasodilative bradykinin and is responsible for cleaving relatively inactive angiotensin I to the potent vasoconstrictor angiotensin II (AT II). Indirectly angiotensin-converting enzyme is responsible for aldosterone production, because AT II is a primary stimulus for adrenal gland production of mineralocorticoids. Given angiotensin-converting enzyme’s critical position in the RAS, it was proposed that angiotensin-converting enzyme inhibition may promote beneficial hemodynamic and neurohormonal antagonistic and antifibrotic actions.

The angiotensin-converting enzyme inhibitor enalapril has been extensively studied in humans with varying stages of heart failure. In three studies, compared with placebo or the combination of hydralazine and isosorbide dinitrate, enalapril reduced all-cause mortality in humans with a reduced ejection fraction and heart failure.

In another study, compared with placebo, enalapril did not reduce the mortality rate in asymptomatic patients with reduced ejection fraction, although it delayed the onset of heart failure. Because angiotensin-converting enzyme inhibitors have been shown to alleviate symptoms, improve patients’ clinical status, and decrease mortality, the current recommendation is that all humans with heart failure due to left ventricular systolic dysfunction receive an angiotensin-converting enzyme inhibitor. The mortality reductions associated with administration of angiotensin-converting enzyme inhibitors lends support to the theory that disease progression is mediated by factors other than hemodynamics alone.

Management of Stable Compensated Congestive Heart Failure

Deficiencies of the Triple Drug Regimen

Potential therapeutic strategies

Management of Refractory Congestive Heart Failure

Management of Heart Failure Secondary to Diastolic Dysfunction

Maintenance Therapy

After stabilization, furosemide is switched to oral administration and the dose is decreased (6.25 mg given twice daily) to prevent excessive preload reduction, dehydration, and hypokalemia. In cases of hypertrophic cardiomyopathy, additional drugs may be instituted to reduce the heart rate and improve diastolic filling. Drugs frequently used in the management of HCM include the beta blocker atenolol and the calcium channel blocker diltiazem. Calcium channel Mockers theoretically can exert a beneficial effect in the management of HCM by modestly reducing the heart rate and contractility, thereby diminishing myocardial oxygen demand. Diltiazem may promote a direct positive lusitropic effect, and verapamil may partially reduce coronary endothelial dysfunction compared with propranolol. Atenolol (6.25 to 12.5 mg given orally every 12 to 24 hours) appears to exert better rate control and more consistently alleviates left ventricular outflow tract obstruction compared with diltiazem. Beta-adrenergic blockade may also prevent myocardial fibrosis by inhibiting catecholamine-induced cardiotoxicity and » may combat ventricular arrhythmias by decreasing myocardial oxygen consumption. One theoretical disadvantage of the use of beta blockers in the management of diastolic dysfunction is that phospholamban is an inhibitory protein that controls the rate of diastolic calcium uptake into the sarcoplasmic reticulum. Beta-adrenergic stimulation phosphorylates phospholamban and removes this inhibitory effect. Beta blockade may prevent this phosphorylation (and therefore decrease diastolic calcium uptake) and further impair the active process of ventricular relaxation.

Similar to beta blockers, with their proposed neurohormonal benefits, angiotensin-converting enzyme inhibitors likely are beneficial in the management of feline HCM. The authors have seen cats with symptomatic cardiomyopathy show marked neurohormonal activation. With this finding, and with the frequent requirement for furosemide to control pulmonary edema, it appears prudent to use enalapril (1.25 to 2.5 mg given orally every 12 to 24 hours) in the management of diastolic dysfunction. Although there is concern that afterload reduction may precipitate dynamic left ventricular outflow tract obstruction, recent data suggest that angiotensin-converting enzyme inhibitors can be used safely in cats with systolic anterior motion of the mitral valve.