Breed Predilections for Acquired Disease

• A degenerative disorder of the left A-V (atrio-ventricular) valve, or mitral valve.
• Common in older small breed dogs, accounting for 75-80% of canine cardiac disease.
• Also known as chronic mitral valvular disease (CMVD), chronic degenerative mitral valve disease (MVD), or endocardiosis.
• Myxomatous degeneration causes thickening and contraction of the valve leaflets, and thickening with lengthening (earlier) or shortening (later) of the chordae tendinae. Myxomatous degeneration is characterized by an increase in the spongiosa layer of the valve and accumulation of glycosaminoglycans. Other features include disruption and fragmentation of collagen fibrils and denudation of overlying endothelium. Inflammation is absent.
• Most dogs with mitral regurgitation also have some degree of tricuspid regurgitation. The tricuspid valve disorder is believed to be the same degenerative process that is affecting the mitral valve that also affects simultaneously the tricuspid valve.
• Inherited in the Cavalier King Charles Spaniel and the Dachshund breeds (polygenetic threshold trait).

Results of CMVI:

1. Mitral regurgitation (MR).
2. Left atrial enlargement with MR.
• Left atrial enlargement and left ventricular enlargement (eccentric hypertrophy) occur due to volume overload. Studying the re-circulation circuit (left atrium and left ventricle in the case of MR) identifies the cardiac chambers that undergo volume overload and eccentric hypertrophy.
3. Right atrial enlargement due to tricuspid regurgitation.
4. Left mainstem bronchial compression due to left atrial enlargement
• Causes cough
5. Supraventricular arrhythmias
• Due to atrial enlargement
• Produces signs of or exacerbation of fluid accumulation
• Pulmonary edema
• Pleural effusion
• Ascites
• Produces syncope/weakness
• Atrial fibrillation
• A common supraventricular arrhythmia
• Often pushes a subclinical case into congestive heart failure
• Often heralds the onset of ascites
6. May cause a tear in the left atrium which usually produces immediate cardiac tamponade
7. Left ventricular (LV) enlargement occurs due to volume overload and pathologic LV remodeling occurs (loss of cardiomyocytes and inadequate hypertrophy)
• Causes eventual myocardial failure and pulmonary edema (congestive heart failure)
• May promote ventricular arrhythmias
8. Rupture of chordae tendinae
• Induces severe and acute pulmonary edema related to sudden increase in left atrial and pulmonary venous pressure
• Chordal rupture occurs in 16% of dogs with CMVI. It increases in frequency in dogs with more advanced disease with the highest prevalence (70%) in dogs with advanced CMVI. (Serres et al. JVIM 2007;21:258-264).
9. Pulmonary artery hypertension secondary to MR can develop and lead to right heart failure
• Pulmonary hypertension occurs in about 30% of dogs with an average systolic pulmonary artery pressure of about 50 mmHg. Note that this included dogs with pre-clinical CMVI. (Borgarelli et al. JVC 2004;6:27-34).

Signalment:

• Geriatric small/toy breeds of dogs
• May occur in other breeds of dogs, including larger breeds (especially the German Shepherd)
• May be inherited in the Cavalier King Charles Spaniel and the Dachshund
• Occurs in males > females, and males may be affected earlier than females

History:

• Usually free of clinical signs
  • Most dogs with CMVI never experience clinical signs related to this disorder. This occurs because the disease is very slowly progressive and it occurs in geriatric dogs at risk for other geriatric disorders that become life limiting prior to the onset of clinical signs of heart disease.
  • Presence of a mitral regurgitation (MR) murmur for months to years prior to onset of clinical signs
  • Coughing
    • May have been present for months
    • Productive or non-productive cough
  • Often no obvious exercise intolerance until in congestive heart failure
  • If heart failure is present, signs typical of congestive heart failure may occur (dyspnea, tachypnea, orthopnea, wheezing, coughing, weakness, exercise intolerance, etc)
  • Syncope may occur in some dogs,
  • May be associated with exertion, excitement, coughing, micturition, defecation
  • Secondary to pulmonary artery hypertension, arrhythmias, or vasovagal syncope
  • Ascites may be present.

Physical Examination:

• Systolic heart murmur of MR (PMI over left apex)
  • If MR is moderate to severe, the murmur tends to continue into and through the second heart sound, obscuring the second heart sound (pansystolic murmur)
  • The severity of MR is related to the intensity of the systolic murmur (grade of murmur).
• A mid-systolic click may be heard in early CMVI
• Arrhythmias are uncommon in the early stage of the disease and may be present late in the disease
• Femoral pulses are often normal
• Cough may be easily elicited on tracheal palpation. This is not an indication of advanced CMVI but is usually related to co-existing tracheal disease particularly tracheal collapse
• Fine crackles, snaps, or popping sounds at end inspiration and early expiration may be heard if pulmonary edema is present. However these sounds may also represent small airway disease.
• If heart failure is present, other signs may be observed (see Clinical Evaluation of Heart Disease section

Comment: When pulmonary hypertension develops, dogs become severely exercise intolerant and syncope is common.

Most cases of CMVI present for some other reason and an incidental heart murmur typical of MR is detected on examination. Those dogs that present for congestive heart failure due to CMVI usually present with a complaint of a cough. Some dogs present with a complaint of syncope.

• In this aged cohort of patients, causes for cough include:
• CMVI with congestive heart failure and pulmonary edema
• Compression of the left mainstem bronchus due to left atrial enlargement from CMVI
• Chronic small airway disease (including collapsing trachea) – potentially the most common cause of cough in this group of dogs
• Our job is to differentiate between these causes of cough

Physical Examination uncovers:

• A systolic murmur typical of MR (see above)
• In the early stages of CMVI this is the only finding on physical exam.
• A systolic click may be present.
• An arrhythmia may be present.
• Pulmonary crackles (or snapping or popping sounds) on auscultation may be indicative of pulmonary edema or small airway disease.
• If heart failure is present, other signs may also be observed (see Clinical Evaluation of Heart Disease).

Radiology may uncover:

• Left atrial enlargement
• Left ventricular enlargement
• Splitting of the main bronchi on lateral view and compression of the left mainstem bronchus
• Peribronchial pattern - the finding of peribronchial changes may indicate either pulmonary interstitial edema or small airway disease. On the basis of the lung pattern alone one may not be able to distinguish between these disorders. If pulmonary venous distension is absent, the peribronchial changes likely reflect small airway disease
• Evidence of heart failure in the case of severe advanced disease
• Pulmonary venous distension, pulmonary edema (peribronchial, interstitial, or alveolar changes, depending on severity) – See Thoracic Radiographic Tutorial
• If acute chordal rupture has occurred, severe pulmonary edema may occur without substantive left atrial or left ventricular enlargement
• If pulmonary artery hypertension is present then pulmonary artery dilation may be observed along with right ventricular and right atrial enlargement.

Electrocardiography may uncover:

• Left atrial enlargement.
• Supraventricular arrhythmia.
• Atrial fibrillation.
• Left ventricular enlargement.
• May be normal. This is typical in the early stages of CMVI.

Blood work:

• Often normal.
• May see signs of reduced cardiac output if heart failure is present
  • Increased urea and/or creatinine (reduced renal perfusion)
  • Elevated lactate
  • Decreased venous oxygen tension (PvO2)
  • Reduced serum sodium
• Brain natriuretic peptide (NT-proBNP) levels increase with increasing severity of CMVI in dogs. NT-proBNP levels may also be predictive of prognosis in humans and dogs with mitral valve disease. See BNP as a Potentially Useful Test in the Clinical Evaluation of Heart Disease section.

Echocardiography:

• Thickened mitral valve leaflets often with prolapse and/or flail of a segment of leaflet. Ruptured chordae may be visualized.
• Doppler detects MR + TR.
• Left atrial enlargement.
• Left ventricular enlargement.
• In the presence of MR, the indices of contractility are falsely elevated. This renders these measures of limited value to assess reduced systolic function. There is evidence to suggest that systolic function is in fact reduced when congestive heart failure develops, though it is more problematic to quantify than in other disorders.
• Larger breed dogs with CMVI are more likely to demonstrate reduced contractility.
• Doppler echocardiography may detect pulmonary artery hypertension along with right atrial and ventricular enlargement.

Summary:

• Left atrial enlargement with compression of the left main bronchus is frequently responsible for cough.
• There is no evidence of heart failure in the early and mid stages of the disorder.
• This is, however, a progressive disorder, and eventually heart failure with pulmonary congestion may develop.
• Acute exacerbation can develop due to rupture of a chordae with severe acute pulmonary edema.
• Left atrial rupture with sudden death rarely occurs.
• Supraventricular arrhythmias may develop, especially atrial fibrillation.
• Ventricular arrhythmias may develop. This could lead to sudden death.
• Pulmonary hypertension can develop, usually in chronic cases.
• These geriatric dogs usually have some degree of chronic small airway disease.

Goals of therapy for CMVI:

1. Prevent the progression to congestive heart failure in dogs in the preclinical stage of CMVI.
   • Only ACE inhibitors have been assessed with respect to delaying the progression of CMVI to the congestive state. In two clinical trials, this class of drug failed to delay the progression of CMVI (SVEP and VETPROOF Trials - see Veterinary Clinical Heart Failure Trials in General Therapeutic Concepts section).
   • No other drug or class of drug has been assessed to address this question.
   • Data from experimentally-induced CMVI suggests:
   • ACE inhibitors may exacerbate the progression of preclinical CMVI
   • Beta blockers may delay the progression of preclinical CMVI. More clinical data is needed to know whether, when, and how to use beta blockers in this disease, however their potential appears promising.

2. Reduce the amount of mitral valve regurgitation:
   • Reduce the regurgitant orifice
   • Repair the mitral apparatus
   • Not readily available in veterinary medicine yet
   • Treatment of choice in people
   • Reduce the size of the left ventricle and thereby shrink the size of the mitral annulus
   • Preload reduction
   • Increase contractility
   • Reduce afterload
   • Reduce the driving pressure that promotes regurgitation
   • This is accomplished by reducing the difference in pressure between the left atrium and left ventricle
   • Reducing the systemic vascular resistance will reduce left ventricular pressure and therefore the difference in pressure between the left atrium and left ventricle
   • Afterload reducers (arterial vasodilators)

3. Reduce left bronchial compression by reducing left atrial enlargement.
   • Arterial vasodilators may reduce the volume of blood regurgitating across the mitral valve and encourage more blood to move out across the aortic valve. With less blood regurgitating across the mitral valve, the left atrium will shrink somewhat and thus reduce left main bronchial compression.
   • Positive inotropes such as pimobendan, at least theoretically, will shrink the annulus of the mitral valve and thereby reduce the amount of regurgitation. This will then reduce left atrial size and hence the amount of compression.
   • The irritation that is encountered by the bronchial tree induces secondary spasm.
   • Bronchodilators may help relieve this problem.
   • Antitussives can help break the viscous cycle of cough-induced coughing.

4. If heart failure is present then therapy should include:
   • Begin with:
   • Furosemide: use the least amount necessary to maintain ease of respiration
   • ACE inhibition
   • Pimobendan
   • Low sodium diet and exercise restriction
   • If the patient remains in CHF or becomes refractory to treatment:
   • Consider increasing the furosemide dose (as long as renal parameters are normal)
   • Consider adding a more potent arterial vasodilator (amlodipine or hydralazine)
   • We find amlodipine rather ineffective to reduce blood pressure in this setting. Hydralazine is very effective to reduce blood pressure in CMVI.
   • Consider increasing the dose of pimobendan
   • Consider adding another diuretic such as a thiazide, if the patient is refractory to high doses of furosemide (and reduce the furosemide dose by half in this case)
   • Consider adding spironolactone (but recognize that it is a relatively weak diuretic given its site of action)
   • As mentioned above, beta blockers may have a role to play in the treatment of this disease. However more clinical data is needed to know whether, when, and how to use this class of drugs in CMVI.
   • Digoxin, in the presence of a sinus rhythm, remains questionable in terms of benefit
   • Supraventricular arrhythmias should be treated as outlined in the Supraventricular Tachycardia section of Electrocardiography
   • Atrial fibrillation should be treated as outlined in the Atrial Fibrillation section of Electrocardiography
   • Acute exacerbation with severe pulmonary edema due to rupture of a chordae is treated as outlined in the Fulminant Pulmonary Edema section of General Therapeutics
   • Pulmonary hypertension if present should be addressed. The most promising arterial vasodilator for pulmonary hypertension is sildenafil (phosphodiesterase V inhibitor), however pimobendan may also be useful in this condition
   • While sildenafil may improve quality of life for patients with pulmonary hypertension it appears that pulmonary artery pressure does not decrease significantly (Kellum et al. JVIM 2007;21:1258-1264)

   Dosages: (canine)

   • Furosemide - 2-4 mg/kg BID – TID (PO)
   • Pimobendan – 0.25 mg/kg BID (on an empty stomach) (PO)
   • Amlodipine – 0.1 mg/kg SID (PO)
   • Hydralazine – 0.5-2 mg/kg BID (PO)
   • Benazepril - 0.5 mg/kg SID to BID (PO)
   • Enalapril - 0.5 mg/kg SID to BID (PO)
   • Hydrochlorothiazide – 1-2 mg/kg BID (PO)
   • Theo-Dur (long acting theophylline) - 20 mg/kg BID (PO)
   • Hycodan - 0.22 mg/kg SID-QID (PO)
   • Sildenafil – 0.5-2 mg/kg BID (PO)

     Management of congestive heart failure involves controlling vascular volume by finding a balance between meeting renal blood flow needs through enhancing vascular volume (preload) and reducing pulmonary edema by reducing vascular volume (preload).

     

1. In the absence of heart failure:
   • CMVI may have a benign course for quite some time in many dogs.
     • The preclinical stage may last for 4-6 years, that is, a murmur of MR can be detected for 4-6 years prior to the onset of clinical signs of congestive heart failure.
     • In a recent large retrospective study of 558 dogs with CMVI, more than 60% of the preclinical (asymptomatic) dogs were still alive 70 months (> 5 years) after the initial diagnosis, and 69% of all the dogs survived or died from causes unrelated to CMVI during the follow-up period which averaged 2 years (Borgarelli et al. JVIM 2008;22:120-128).
   • In a clinical trial of Cavalier King Charles Spaniels with preclinical CMVI (all at various stages), the average time to CHF after enrolment was 3 years (Kvart et al. JVIM 2002;16:80-88).
     • The intensity of the heart murmur was related to the size of the heart and inversely related to the time to onset of heart failure.
     • The louder the heart murmur and the larger the heart, the sooner heart failure will develop.
   • Other factors that appear to be related to prognosis in the asymptomatic phase include breed, age, family history, presence of mitral valve prolapse, and indices of heart size including vertebral heart score (VHS) and left atrium:aorta (LA:Ao) ratio on echocardiography.
   • Sudden death has been reported infrequently in preclinical CMVI dogs (5/302 preclinical dogs = 1.6% in Borgarelli’s study above)
   • Large breed dogs as compared with small breed dogs with CMVI tend to:
     • Have a greater degree of depressed contractility
     • Have less mitral valve insufficiency
     • Have less thickening and prolapse of the mitral leaflets
     • Have lower intensity heart murmurs
     • Be more likely to manifest atrial fibrillation
     • Be of the same age
     • Have the same survival

2. If congestive heart failure is present:
   • Symptoms can be controlled and exercise tolerance increased but animals usually succumb to this disorder within 2-3 years. Some dogs experience repeated bouts of acute heart failure. This may occur due to the development of an arrhythmia, excessive exercise, excessive sodium load, or rupture of a chordae tendinae. Frequently, these bouts of acute pulmonary edema can be stabilized, and these patients returned to the previous level of activity.
   • In Borgarelli’s retrospective study of 558 dogs with CMVI cited above, the median time to cardiac-related death was 33 months in dogs with mild to moderate heart failure and 9 months in dogs with advanced heart failure.
   • Factors related to poorer prognosis in the above study included increased age, presence of syncope, presence of arrhythmias, increased heart rate, increasing left ventricular size, presence of ascites, plasma urea concentration and the strongest predictor of all, increasing left atrial size.

3. If pulmonary hypertension develops:
   • There are no good studies assessing the effect of pulmonary artery hypertension independent of other factors.
     • One study suggests it has no effect on survival.

4. If ruptured chordae develops:
   • With therapy for acute fulminate pulmonary edema, many patients can be returned to compensation within 5 days. Their outcome can still be good with survival for another year or more.
   • In a retrospective study of 57 dogs with chordal rupture, the median survival time was 425 days after diagnosis, with 58% surviving > 1 year (for the dogs in whom follow-up was available) (Serres et al. JVIM 2007;21:258-264). This suggests that chordal rupture may not be as devastating a consequence of CMVI as previously speculated.

Cardiomyopathy refers to a primary global disorder of the myocardial tissue.

Classically cardiomyopathy is divided into several types with the two most common being:

1. Dilated Cardiomyopathy (DCM), characterized by:

1. Systolic dysfunction (decreased muscle strength/decreased contractility)
2. Ventricular cavity dilation (eccentric hypertrophy)
3. Mild thinning of the ventricular walls
4. Total ventricular mass is increased
5. Well recognized in the cat and dog
6. Etiology is often unknown in dogs
• Likely genetic (familial) in many cases
• A mutation in the titin protein gene may be responsible for DCM in Doberman Pinschers
• A number of genetic mutations have been identified in humans with familial DCM
• Due to a deficiency of taurine in some Cocker Spaniels
• In some cases a deficiency of carnitine has been reported to be responsible for dilated cardiomyopathy (a family of Boxers)
• A morphologic picture of DCM can be induced by tachyarrhythmias, certain chemotherapeutics (e.g. doxorubicin), and myocarditis
7. A deficiency of taurine was previously responsible for the vast majority of cases of dilated cardiomyopathy in cats. It is not likely involved in feline DCM in cats on commercial cat food.

2. Hypertrophic Cardiomyopathy (HCM), characterized by:

1. Diastolic dysfunction (impaired relaxation)
2. Ventricular cavity of diminished dimension
3. Thickening of the ventricular walls (concentric hypertrophy)
4. Increased ventricular mass
5. Well recognized in the cat
6. Rare in the dog
7. Etiology unknown in most cats
• In many cats it appears to be familial and inherited as autosomal dominant
• In Maine Coon and Ragdoll cats, mutations of the cardiac myosin binding protein C gene are involved
8. Hypertension and thyrotoxicosis can induce a morphological picture of concentric hypertrophy. Growth hormone excess may cause concentric hyptertrophy.
9. HCM has been subcategorized into an obstructive form and a non-obstructive form

Most cases are idiopathic. That is, the processes or insults ultimately leading to the morphologic diagnosis of DCM are unknown in most cases. As the heart has a limited number of responses to a variety of insults, the diagnosis of DCM often gives little to no insight into the underlying etiology with few exceptions.

• Taurine deficiency in some Cocker Spaniels.
• Taurine deficiency in some cases of unusual breeds (non giant breeds, non Dobermans).
• A mutation of the titin gene in Doberman Pinschers, in which the disease appears to have autosomal dominant inheritance.
• Tachycardia-induced. Any tachycardia (>240 bpm for >3 weeks) will cause a DCM-like picture.
• Doxorubicin-induced.
• Viral induced. We believe some cases of acute DCM might be viral-induced, particularly in young dogs.
• Role of carnitine: Work performed by Dr. Bruce Keene a number of years ago suggested that a deficiency of carnitine may be responsible for DCM in some Boxers. Carnitine is essential to transport fatty acids into the mitochondria of the muscle cell. Without adequate carnitine, fatty acids cannot enter the mitochondria, and energy deficiency results. However, carnitine presently does not appear to be responsible for most cases of DCM observed in Boxers or other breeds. Rather carnitine deficiency is likely a secondary effect in heart disease and not a primary cause.

Signalment:

• Mainly occurs in giant and large breeds
• In the enalapril trials in the 90’s that recruited dogs with DCM throughout North America, 54% of all dogs with DCM were Doberman Pinschers. Thus, DCM, at present, is more common in the Doberman than in all breeds of dogs combined.
• Also seen in Cocker Spaniels
• Ultimately may occur in almost any breed
• Tend to be middle-aged to older individuals. The exception is a juvenile form of DCM in Portuguese water dogs
• More frequent in males in some studies

 History:

• Frequently present for sudden development of dyspnea, wheeze or cough
• Cough was noted in 72% of dogs at time of presentation for CHF (Bronsoiler J Thesis 2005)
• Also may find:
• Weight loss
• Anorexia
• Cool extremities
• Exercise intolerance/weakness
• Syncope - noted in 16% of dogs at presentation for CHF
• Restlessness at night/orthopnea
• Abdominal distention
• Ascites was noted in 14% of dogs at time of presentation for CHF (Bronsoiler J Thesis 2005)
• Some individuals expectorate a serosanguinous fluid (indicative of severe pulmonary edema and potentially signaling that death may be imminent)
• Sudden death is common (in the Doberman this may account for up to 30% of cases).

Physical examination:

• All the possible findings of congestive heart failure as per the physical examination findings in heart failure
• Arrhythmias, primarily ventricular, are common; also atrial fibrillation.
• Pulse deficits, if an arrhythmia is present
• Systolic heart murmur of mitral regurgitation (due to dilation of the mitral annulus) (PMI at left heart apex).
• A heart murmur was noted in 82% of dogs at the time of presentation for CHF
• The median grade of the heart murmur was 3/6
• S₃ and or S₄ gallop sounds are very common in these cases.
• A gallop was noted in 60% of dogs at the time of presentation for CHF
• Increased lung sounds, tachypnea
• Inspiratory crackles were noted in 33% of dogs at the time of presentation for CHF (Bronsoiler J Thesis 2005)

The definitive diagnosis of canine DCM is by echocardiography with the demonstration of ventricular dilation and reduced contractility (systolic dysfunction).

In the absence of echocardiography, usually presumptive evidence of canine DCM can be obtained:

a) Radiology:

• Pulmonary venous congestion/pulmonary edema in cases of CHF
• Left ventricular enlargement
• Left atrial enlargement
• Pleural effusion - noted in 21% of dogs at the time of presentation for CHF (Bronsoiler J Thesis 2005)

b) Electrocardiography: may reveal:

• May be normal
• Infrequent to frequent ventricular arrhythmias
• VPCs were observed in 84% of giant breed dogs, 76% of large breed dogs, 58% of Spaniels, and 82% of Dobermans at the time of presentation for CHF (Bronsoiler J Thesis 2005).
• Supraventricular premature beats, especially atrial fibrillation
• Atrial fibrillation was observed in 76% of giant breed dogs, 35% of large breed dogs, 11% of Spaniels, and 38% of Dobermans with CHF (Bronsoiler J Thesis 2005).
• Left ventricle enlargement
• Left atrial enlargement
• ST segment depression
• Wide QRS duration
• Microscopic intramural myocardial infarction (MIMI) (notch in the QRS complex)

Note: none of these findings are diagnostic of canine DCM

c) Blood Work:

• Evidence of reduced cardiac output as per Bloodwork in Clinical Evaluation of Heart Disease
• A deficiency in plasma taurine may occur in Cocker Spaniels and other dogs
• A deficiency in plasma carnitine may occur in giant breed dogs and boxers
• Elevated cardiac Tn-I

Therapy with an ACE-inhibitor is recommended in preclinical (occult) DCM. There is substantive evidence in humans and retrospective evidence in dogs that ACE-inhibitor therapy delays the onset of CHF, likely by altering ventricular myocardial remodeling. Time to onset of clinical signs of CHF when one treats Dobermans in the preclinical (occult) stage of DCM with benazepril results in a 25% increase in the time to onset of clinical signs of CHF (O’Grady & O’Sullivan et al. JVIM 2009;23:977-983). No other drugs have been assessed in this stage of DCM.

For the patient with CHF secondary to DCM, treatment is as per congestive heart failure in the General Therapeutic Concepts section.

• Begin with:
• Furosemide: use the least amount of diuretic (furosemide) to maintain ease of respiration
• Pimobendan
• ACE inhibition
• Low sodium diet and severe exercise restriction
• If substantive pulmonary edema remains or the patient becomes refractory to treatment, then consider:
• Increasing the dose of furosemide (as long as renal parameters are normal)
• Increasing the dose of pimobendan
• Adding spironolactone (but recognize that this is a weak diuretic given its location of action in the nephron)
• Adding another diuretic such as a thiazide if the patient is refractory to high doses of furosemide
• The combination of diuretics is very potent and profound hypotension can develop. We reduce the furosemide dose by about 50% when we add the thiazide then uptitrate as necessary.
• Adding a more potent arterial vasodilator (amlodipine or hydralazine)
• The utility of digoxin, in the presence of a sinus rhythm, remains questionable
• Supraventricular arrhythmias should be treated as outlined in the Supraventricular Tachycardia section of Electrocardiography
• Atrial fibrillation should be treated as outlined in the Atrial Fibrillation section of Electrocardiography
• Ventricular arrhythmias are treated as per Questions 31 and 32 in the Electrodariology section
• Those cases demonstrated to possess a taurine deficiency (as with the American Cocker Spaniel) should receive 500 mg PO BID of taurine in addition to ACE inhibitors, pimobendan, and diuretics.
• Those cases demonstrated to possess a carnitine deficiency (if proof is definitive) should be supplemented with carnitine at 150 mg/kg PO divided BID in addition to pimobendan, ACE inhibitors, and diuretics.

Dosages: (canine)

• Furosemide – 2-4 mg/kg BID – TID (PO)
• Pimobendan – 0.25 mg/kg BID (on an empty stomach) (PO)
• Benazepril - 0.5 mg/kg SID to BID (PO)
• Enalapril - 0.5 mg/kg SID to BID (PO)
• Amlodipine – 0.1 mg/kg SID (PO)
• Hydralazine – 0.5-2 mg/kg BID (PO)
• Spironolactone – 1-2 mg/kg BID (PO)
• Hydrochlorothiazide – 1-2 mg/kg BID (PO)

  Management of congestive heart failure involves controlling vascular volume by finding a balance between meeting renal blood flow needs through enhancing vascular volume (preload) and reducing pulmonary edema by reducing vascular volume (preload).

  Comments:

• Pimobendan is definitively proven to improve survival for these patients in CHF.
• Although ACE inhibitors have not been proven to improve survival (Bench and Live Trials), we continue to use these drugs as evidence of their benefit in people with DCM is overwhelming.
• We do not use digoxin routinely in these cases.
• Beta blocker therapy has been demonstrated in people with CHF due to DCM to be essential. It definitively increases survival when added to an ACE inhibitor and diuretic. There are no treatment trials in dogs with DCM (whether in CHF or not) assessing the role of beta blockers

Survival data involving 275 dogs with DCM studied over 20 years at the OVC (Bronsoiler J et al JVIM 2005;19:204.):

• Giant breed dogs (45 dogs): Median survival time of 91 days
• Large breed dogs (37 dogs): Median survival time of 137 days
• Spaniels (19 dogs): Median survival time of 330 days
• Doberman Pinschers (174 dogs): Median survival time of 42 days
• Now with the use of pimobendan and ACE inhibitors in Doberman Pinchers survival is 4-6 months
• Presence of atrial fibrillation significantly reduces survival in dogs with CHF due to DCM
• Presence of VPCs increases both overall death and risk of sudden death.
• Sudden death is more common in Doberman Pinschers than the other groups
• Sudden death is least common in the Spaniel group

This disorder is morphologically identical to canine DCM. It is characterized by eccentric hypertrophy and global hypokinesis (systolic dysfunction). Unlike the disorder in dogs, the potential to develop concurrent thromboembolic complications is frequent in cats.

Taurine deficiency induced DCM was previously a common cause of feline cardiac disease. With the addition of taurine to the commercial feline diets, taurine deficiency-induced DCM is now rare.

• Cats have a taurine sink due to hepatic conjugation using taurine, whereas dogs use glycine for hepatic conjugation
• Most commercial cat foods have increased their level of dietary taurine at least 10 fold, therefore, DCM is now a rare disorder
• A taurine deficiency is not responsible for feline hypertrophic cardiomyopathy.

Signalment:

• Usually middle aged to older adults
• Burmese, Siamese, and Abyssinians may be predisposed.

History:

• The first sign of underlying heart disease may be the development of a sudden thromboembolic event to one of the limbs (usually both hind limbs).
• Dyspnea is the most frequent complaint
• Syncope is an infrequent presenting sign
• Anorexia, lethargy, and/or sometimes vomiting may be noted
• These signs usually are noted to have a recent onset prior to presentation

Physical Examination:

• Marked dyspnea is usually present (due to pulmonary edema or pleural effusion)
• All the possible findings of congestive heart failure as per Question 2 of Clinical Evaluation of Heart Disease
• Ascites which is common in dogs, tends to be rare in cats
• Gallop rhythms are more common in cats
• Heart murmur of A-V valve insufficiency is common
• Dysrhythmias tend to be more uncommon than in dogs
• Due to the pleural effusion, heart sounds may be muffled
• Hypothermia tends to be common
• Evidence of thromboembolism may be noted (see question 19 below)

A definitive diagnosis is possible with echocardiography (a dilated, relatively thin-walled left ventricle with reduced contractility).

Among acquired feline heart disorders, dilated cardiomyopathy and hypertrophic cardiomyopathy used to be the most common disorders, and the diagnostic challenge was to distinguish between these two forms of cardiomyopathy. Since the introduction of routine supplementation of taurine to the feline commercial diets, dilated cardiomyopathy has become a rare disorder. Thus, the hypertrophic (concentric hypertrophy) form is the most common type of cardiomyopathy presently occurring in the cat.

Other potentially useful diagnostic aids:

a) Radiology:

• Pleural effusion is often present and obscures the cardiac silhouette
• A diffusely enlarged, rounded heart is often noted. However the sensitivity and specificity of this finding are relatively low (especially specificity) in that many cases of hypertrophic cardiomyopathy can show this type of radiographic picture
• Typical findings of congestive heart failure may be present (see Question 6 in the Thoracic Radiography Tutorial section)

b) Electrocardiography: may reveal

• A normal ECG
• Tall R waves in lead II
• Ventricular ectopy

 c) Blood Work:  may reveal

• Evidence of reduced cardiac output as per Bloodwork (Question 28) in the Clinical Evaluation of Heart Disease section
• Serum taurine levels may be low
• Muscle enzyme elevation if thromboembolism occurs
• Troponin I is likely elevated
• NT-proBNP is likely elevated

Goals of therapy:

1. Treat pulmonary edema/pleural effusion:
• Thoracocentesis
• Furosemide
• Venodilator therapy (nitroglycerine cream)
• If cat is being treated with corticosteroids, attempt to discontinue corticosteroid use as they promote fluid retention.
2. Augment systolic dysfunction
• ACE inhibitors
• efficacy undetermined in cats
• Pimobendan
• safety and efficacy undetermined in cats
• Arterial vasodilators (non-ACE inhibitors)
• safety and efficacy undetermined in cats
3. Prevent thromboembolic disease
• See section addressing thromboembolism below
4. Treat the underlying etiology
• Taurine supplementation 250 to 500 mg PO (BID) if taurine deficiency is suspected
5. Other measures
• Low sodium diet (watch for refusal to eat)
• Restrict activity

• Without taurine supplement, the vast majority of cases die within 2 months with aggressive therapy for congestive heart failure
• With taurine supplementation, if cardiac function can be sustained for 4 to 6 weeks, the prognosis for complete recovery would appear to be excellent

• Cats with 4 chamber dilation and diffuse hypokinesis have an abysmal prognosis. Expect death in 2 weeks in spite of therapy.

Thromboembolic disease (TED) is an important and relatively frequent complication of feline myocardial disease. Thrombosis represents clot formation within a cardiac chamber or vessel, and embolization occurs when a clot fragment lodges in a distal vessel. In the case of feline TED, the clot fragment usually arises from atrial thrombi or from atrial lesions and most commonly embolizes to the distal aortic trifurcation. Other less frequent sites of embolization include brachial, renal, celiac, and cerebral arteries. TED is frequently the first sign of underlying cardiomyopathy.

In a recent retrospective study of 127 cats with arterial thromboembolism (ATE), it was the first sign of cardiac disease in 76% of affected cats.

Physical occlusion of the aorta alone will not cause this syndrome. Vasoactive substances released by the thrombus/endothelium are believed to cause vasoconstriction of collateral vessels. Serotonin and prostaglandins are the likely vasoactive agents. This causes ischemic damage to peripheral nerves, muscle and sometimes skin.

The presence of a thromboembolic event usually indicates the existence of underlying cardiac pathology. Typically cardiomyopathy and left atrial enlargement are present. However, we and others have observed cats without obvious cardiomyopathy and without left atrial enlargement experience a thrombotic event. Neoplasia and hyperthyroidism (even in the absence of cardiac changes) are disorders with which TED has also been associated.

1. History:

• Acute onset of posterior paresis with:
  • Extreme pain
  • Hard/firm muscle groups in the affected legs
  • It is not uncommon for this to be the only clue to the presence of cardiomyopathy
  • Other signs of feline cardiomyopathy (dilated or hypertrophic) may be present

2. Physical Examination:

• Lower motor neuron paralysis of the affected limb with
  • Lower motor neuron sensorimotor neuropathy
  • Extreme pain
  • Firm muscle groups
  • Cyanotic nail beds
  • Weak to absent arterial pulse in limb
  • Cool to palpation
  • Failure of nail beds to bleed with short clipping
• May have signs of feline cardiomyopathy (dilated or hypertrophic) as per above
• Gallop cardiac rhythms and murmurs of AV valve insufficiency are frequently encountered, however it is reported that as many as 40% of cats with ATE may not have auscultable abnormalities.
  

3. Other diagnostic aids:

• As for feline cardiomyopathy depending on type
• Blood work indicates muscle necrosis (elevated CK and AST)
• Acute renal failure, metabolic acidosis, DIC, or hyperkalemia
• Blood work may indicate reduced GFR
• Blood work may indicate hyperthyroidism

4. Therapy:

• Surgery is not a real consideration.
  • Removal of the clot will not reverse the collateral circulatory "shut down" and anesthesia is very risky in these patients

• Medical therapy
• Inhibit clot formation
  • Aspirin to prevent further thromboembolic events. As a cyclooxygenase inhibitor, it prevents formation of thromboxane thus preventing platelet aggregation.
  • Low dose ASA (5 mg/cat q 3 days) vs high dose ASA (81 mg/cat q 3 days)
  • There is some evidence to suggest that the low dose may be preferred to the traditional high dose.
  • Clopidogrel – 18.75 mg/cat SID (PO). Clopidogrel is a platelet function inhibitor that appears, in a limited study, to be safe and effective in cats.
  • Clopidogrel is safer and more effective than ASA in people
  • Results of a trial investigating the use of aspirin vs clopidogrel in cats with TED will be forthcoming (FATCAT trial).
  • Heparin may be useful (to prevent further thromboembolic events) – 200 units/kg IV as a loading dose followed 4 hours later by 150-200 units/kg SQ after obtaining ACT or PTT, May repeat again at 8 hours after obtaining ACT or PTT. Goal is 1.5-2 times increase in the pre-heparin ACT or PTT result. Once this is achieved, reduce to 100-150 units/kg Q 8 hours. Must monitor closely for hemorrhage. Heparin will not lyse the existing clot, but will prevent further clot formation via its anticoagulant effects. By enhancing antithrombin III activity, it inhibits coagulation factors II, IX, X, XI, and XII.
  • Low molecular weight heparin (LMWH) is an alternative to regular unfractionated heparin (UH). LMWH has higher bioavailability, longer half-life, less protein binding, and more predictable effects than UH. As such, LMWH is potentially easier and safer to use than UH. Because of its' different structure, LMWH selectively inhibits factor X and does not prolong coagulation times. It is administered subcutaneously once to twice daily (see formulary for doses).
• Pain management is a very important part of therapy. Opioids such as morphine, butorphanol, or fentanyl patches are typically used.
• Supportive care: nutrition, warming, physical therapy, prevention of self-mutilation
• Thrombolytic therapy with enzymes such as streptokinase and tissue plasminogen activator (TPA) has been used with some success to dissolve thromboembolic episodes. These agents can be quite expensive. Since many cases recover spontaneously due to recanalization or collateralization, studies are lacking to demonstrate an improvement with these agents over placebo. Use of TPA has demonstrated a 50% resolution of thrombi with ambulation in 48 hours of treatment. However, 50% died during therapy (due to hyperkalemia and metabolic acidosis [reperfusion syndrome] in 70%).
• Treatment of concurrent CHF and/or malignant arrhythmias may also be necessary.
• It is important to monitor respiratory status, heart rhythm (ECG), renal function, electrolytes (especially potassium), temperature, and mobility.

5. Prognosis:

• With complete aortic occlusion: 35% survive initial episode
• With suprarenal aortic thrombosis: grave prognosis due to acute renal failure, GI ischemia, spinal cord dysfunction and degeneration
• Partial embolization: 70% survive initial episode
• Spontaneous resolution occurs in over 50% of cases within 2 to 6 weeks.
• The recurrence rate of re-embolization appears to be high, usually within 6 months (with ASA).
• In one study of 100 cases (Laste et al. JAAHA 1995):
  • 63% died or were euthanized during hospitalization
  • 37% survived to live a median of 10 months, ave = 11.5 months
  • Re-embolization occurred in 50% of survivors
• In another more recent study of 127 cases (Smith et al. JVIM 2003):
  • 65% died or were euthanized during initial hospitalization
  • 35% survived (discharged) to live a median of 117 days (about 4 months)
  • Re-embolization occurred in 25% of survivors
• Persistence of low rectal temperature is associated with a poor short-term prognosis.
• Others report that survival is related to presence of co-morbid factors:
• If there is no concurrent CHF – median survival time = 225 days
• If CHF is also present – median survival time was
  • 77 days in one study
  • 184 days in another

6. Prophylaxis:

• Aspirin (81 mg/cat q 3 days or twice weekly) has been recommended for all cats with an enlarged left atrium, however there is no data to indicate if aspirin is any better than placebo.  There is some evidence to suggest that low dose aspirin (5 mg/cat Q 3 days) is equally as efficacious with fewer side effects. Clearly many cats have recurrent bouts of thrombosis while on aspirin.
• Clopidogrel 18.75 mg/cat Q 24 hours has recently been advocated for thromboprophylaxis in cats. The results of a trial (FATCAT) comparing aspirin vs clopidogrel in cats with ATE should be forthcoming.
• Heparin enhances antithrombin III activity.  Close monitoring for severe hemorrhage is necessary.  Seek a 1.5 to 2 times increase in PTT above preheparin levels.  Hemorrhage can be reversed with protamine sulfate.
• Coumarin (warfarin) inhibits synthesis of Vitamin K dependent clotting factors (II, VII, IX, & X).  It will take about 3 days for coumarin to be effective (the delay needed for existing clotting factors to decline).  Dose: 0.06 - 0.1 mg/kg q 24 hours PO.  Monitor response via PT on day 0, 1, 2, 3, 5, 7, 10, 14, 21, 35, q 4wks.  Vitamin K1 will reverse coumarin overdose.  During the first three days of therapy patients may be in a "hypercoagulable state".  Some recommend concurrent use of heparin during this time. There is no clinical evidence to support that warfarin is superior to aspirin in the prophylaxis of ATE.
• As mentioned above, low molecular weight heparin (LMWH) may prove to be a safer alternative than heparin or coumarin in ATE prophylaxis. Dosage and efficacy are currently being evaluated.

Hypertrophic cardiomyopathy (HCM) is an acquired idiopathic myocardial disorder characterized by concentric hypertrophy and resultant diastolic dysfunction of primarily the left ventricle. It is the most common type of cardiomyopathy in cats.

The majority of cases are idiopathic, that is, the primary etiology is unknown. Like in humans, a familial and heritable form of HCM has been identified in certain feline breeds, including families of Maine Coons, Ragdolls, Persians, American Shorthairs, and British Shorthairs. The mode of inheritance in these breeds appears to be autosomal dominant. Breed-specific mutations of the myosin binding protein-C gene have been identified as causative of HCM in Maine Coons and Ragdolls. It is known, however, that there are other undiscovered genetic mutations since not all positive cases are linked to the above mutations.

While most cases are idiopathic, HCM may be secondary to other disorders such as:

• Systemic arterial hypertension
• Hyperthyroidism

  a) Signalment:

• Middle aged cats, at times young adults may present
• Males may be more frequently affected than females
• Persians, Maine Coons and Ragdolls may be predisposed

  b) History:

• Sudden development of dyspnea
• Anorexia
• Lethargy/weakness
• Syncope
• Limb paralysis if thromboembolic disease occurs
• Sudden death may occur (and may be the first sign of disease)
• Free of clinical signs; discovered in cats free of clinical signs when a heart murmur or gallop detected on physical examination was pursued

  c) Physical Examination:

• Signs of congestive heart failure as outlined in Question 2 of Clinical Evaluation of Heart Disease section
• Abdominal effusion is rare; pleural effusion is common
• Dysrhythmias, pulse deficits
• If thromboembolic disease occurs
• Paralysis of the affected limb - usually a hindlimb
• The muscle is hard, painful and cool
• There is a weak or absent arterial pulse in the limb
• A shortly clipped toe nail in the affected limb may fail to bleed
• May be the first and only presenting sign of underlying cardiomyopathy of any type
• Gallop cardiac rhythms are frequent
• A systolic heart murmur of mitral insufficiency and/or left ventricular outflow obstruction may be present
• Note that the absence of a murmur or a gallop does not rule out the presence of HCM. In a recent study, 22% of cats with HCM had neither a murmur nor a gallop on physical examination.

The definitive diagnostic test for feline HCM is echocardiography with the demonstration of thickening of the interventricular septum and/or left ventricular free wall with normal to reduced left ventricular chamber size and normal to enhanced contractility.

  a) Auscultation: may find

• Systolic heart murmur of mitral valve insufficiency and/or left ventricular outflow tract obstruction
• Gallop (typically an S4 gallop)
• Dysrhythmia
• Muffled heart sounds (usually due to pleural effusion)

  b) Radiology:

• The appearance of the heart on the D/V or V/D view has been described as "valentine-shaped" with mild cardiomegaly
• However, at least 50% of the cases have more generalized cardiomegaly typical of feline dilated cardiomyopathy.  Furthermore, many cases of feline dilated cardiomyopathy have cardiac silhouettes that look somewhat valentine shaped.   In conclusion, radiographic appearance of the cardiac silhouette on the V/D or D/V view is unreliable
• Pleural effusion is common which obscures the cardiac silhouette
• Other findings typical of congestive heart failure may be found (see Thoracic Radiographic Tutorial section)

  c) ECG:

• May be normal
• May have evidence of a left shift of the MEA in the frontal plane (-30 to -60 degrees)
• May have a left ventricular enlargement pattern (tall R wave)
• A dysrhythmia may be present (ventricular premature contractions are most common)
• Microscopic intramural myocardial infarction (MIMI) may be present (notch in the QRS complex)

  d) Blood work:

• As per congestive heart failure (see Question 28 in Clinical Evauluation of Heart Disase section)
• Elevated BUN or creatinine, or abnormal fundic examination may suggest systemic arterial hypertension
• Elevated T4 (if HCM is due to concurrent hyperthyroidism)
• NT-proBNP levels show great promise in the diagnosis of occult (preclinical) HCM and in the differentiation of CHF from respiratory disease in dyspneic cats. See Question 29 in Clinical Evaluation of Heart Disease section for more info.
• DNA tests for the myosin binding protein-C mutations are available for Maine Coons and Ragdolls through Dr. Kate Meur’s cardiac genetics lab at Washington State University (http://www.vetmed.wsu.edu/deptsVCGL/index.aspx)

  e) Echocardiography:

• Left ventricular concentric hypertrophy (thickening of the interventricular septum and/or left ventricular free wall (>6mm) with a normal to reduced left ventricular cavity).  This increased LV wall thickness may be diffuse or focal.  If focal it may affect only the interventricular septum, apex or free wall.
• Feline HCM can be divided into obstructive and non-obstructive HCM.
• Obstructive HCM is a common variant wherein the left ventricular outflow tract (LVOT) is obstructed by the abnormal anatomy of the interventricular septum (IVS) that encroaches into the LVOT (dynamic outflow tract obstruction) with or without an abnormal action of the anterior leaflet of the mitral valve which may also encroach on the LVOT during systole. The obstructive form of HCM is characterized by turbulence and increased velocity of blood flow across the LVOT.
• Non-obstructive HCM is a variant that does not involve obstruction of the LVOT.  In this form, the left ventricular wall (LVFW) and IVS may be symmetrically thickened or there may be only focal thickening of the walls of the left ventricle involving only the IVS, LVFW or apex of the LV. There is no increased velocity of blood flow across the LVOT.
• Left atrial enlargement and mitral valve insufficiency are common.
• Pleural effusion or pericardial effusion may occur.

 
Comment:  As cardiomyopathy is frequently an incidental finding in otherwise symptom-free cats, we recommend that all cats with heart murmurs or a gallop rhythm undergo an echocardiographic examination.

Recall: The underlying disorder is one of severely impaired left ventricular filling (diastolic dysfunction) due to increased wall thickness, impaired ventricular relaxation, and the development of ischemic induced myocardial fibrosis (increased ventricular stiffness). Systolic function is relatively preserved (at least until late in the disease process).

Principles of therapy:

1. With respect to the obstructive form of HCM we traditionally expect the following hemodynamic changes to reduce the degree of obstruction

• A decrease in contractility
• A decrease in heart rate
• An increase in preload
• An increase in afterload

2. Attempt to improve left ventricular diastolic function (as ventricular filling is improved, stroke volume will increase and therefore pulmonary edema will decrease)

Beta-blockers improve diastolic function indirectly by reducing heart rate and improving myocardial perfusion, thereby enhancing ventricular filling. Their negative inotropic properties reduce myocardial oxygen demand/consumption and thus may reduce ischemia. Beta-blockers also have antiarrhythmic properties that may be of benefit in this disorder. Beta-blockers reduce or abolish dynamic LVOT obstruction, and are therefore often used in the obstructive form of HCM. And finally, blockade of the deleterious effects of chronic sympathetic nervous system activation (vasoconstriction increasing afterload, myocardial necrosis, coronary vasospasm, arrythmogenesis) may be of benefit. Beta-blockers are the therapy of choice in humans with obstructive HCM or with exertional dyspnea and exercise intolerance.

• Atenolol: 6.25-12.5 mg/cat SID-BID (PO)
• Metoprolol: 0.5-1 mg/kg TID (PO)

Calcium channel blockers, like beta blockers, reduce heart rate and myocardial oxygen consumption. They also may improve the active process of myocardial relaxation directly. In humans and in cats, the tendency in the past was to treat non-obstructive HCM with calcium channel blockers (diltiazem). However the most recent therapeutic consensus guidelines for human HCM do not include the use of calcium channel blockers as there is no conclusive evidence that calcium channel blocker improve symptoms, hemodynamics, or survival.

• Diltiazem: 1-2 mg/kg TID (PO) or 7.5 mg per cat TID

Angiotensin converting enzyme (ACE) inhibitors - Traditionally, treatment of HCM has focused on negative inotropic/chronotropic therapy (beta blockers, calcium channel blockers), and ACE inhibitors have been avoided (particularly in obstructive HCM) due to the impression that any arterial vasodilation may promote hypotension. However, the renin-angiotensin-aldosterone system (RAAS) plays an important role in stimulation of myocardial hypertrophy and fibrosis (which adversely affects diastolic function) and progression of heart failure. Therefore ACE-inhibitors may theoretically have some benefit in the setting of HCM. Recent work in veterinary medicine suggests that ACE-inhibition does not worsen dynamic LVOT obstruction or promote hypotension in HCM cats and that ACE-inhibitors are tolerated well in this population. Interim analysis of an ongoing prospective randomized clinical trial of therapy in feline CHF due to HCM suggests that cats treated with ACE-inhibitors tend to have a better outcome (not statistically significant) than those treated with either beta-blockers or calcium channel blockers. As the final results of this trial have yet to be published, any conclusions at this point are premature. However in the asymptomatic (pre-CHF) stage of HCM, two recent placebo-controlled feline studies showed no improvement in LV wall thickness, mass, or diastolic function with ACE-inhibitor therapy for 6-12 months (MacDonald et al JVIM 2006, Taillefer et al CVJ 2006). Note also that ACE-inhibitors are not featured in the most recent therapeutic consensus guidelines for human HCM.

3. Reduce pulmonary edema and pleural effusion for cats in CHF:

• Diuretics - furosemide (Lasix): 1-2 mg/kg BID-TID (PO, IM, IV); do not exceed 2 mg/kg (IV)
• Although diuretics are very useful initially when pulmonary edema is present, as pulmonary edema resolves and additional therapy is in progress, one should attempt to use the least diuretic dose/reduce the dose (these individuals require as much preload as possible to prime their stiff left ventricle). Dramatic improvement may be noted with conservative doses.
• ACE-inhibitors likely have a role to play in the management of CHF by blocking the RAAS when furosemide therapy is used
• enalapril or benazepril: 0.25-0.5 mg/kg Q 24 hrs PO
• Renal parameters and electrolytes must be monitored
• Periodic thoracocentesis for pleural effusion may be necessary

4. Direct arteriolar dilators will potentially exacerbate the situation; they reduce afterload and can promote hypotension as the left ventricle (already contracting maximally) cannot substantially augment stroke volume to raise blood pressure. Don't use them.

5. Prevent thromboembolic disease. See Question 19 above.

6. Treat underlying disorders if present.

• Hyperthyroidism - see Question 32 for management.
• Systemic hypertension - it is important to rule out hypertension as etiologic.

• Median survival time (MST) overall was 732 days.
• Cats free of clinical signs lived much longer (MST 1830 days) than cats with heart failure (MST 92 days).  Cats with heart failure lived longer than cats with thromboembolism (MST 61 days).
• Cats with an initial heart rate > 200 did worse than if heart rate < 200.

• Median survival time overall was similarly 709 days.
• MST for cats free of clinical signs was 1129 days, while MST for cats with clinical signs was as follows: 654 days for cats with syncope, 563 days for cats with CHF, and 184 days for cats with ATE. The longer survival times for cats with clinical signs in this more recent study may be due to changes over time in the natural history of disease, differences in disease severity, or improvements in medical therapy.
• Increasing left atrial size and age were associated with shorter survival times

Feline restrictive cardiomyopathy refers to that group of primary myocardial disorders that are not typical of feline DCM or feline HCM.  Morphologically the heart is characterized by a normal to reduced contractility, no thickening of the interventricular septum or LV free wall, a normal to small left ventricular cavity potentially with a thickened endocardium, and marked atrial enlargement (often bilateral).

The history and physical examination are identical to those of feline HCM.  The diagnosis relies on the echocardiographic examination. Doppler echocardiography demonstrates abnormal transmitral flow, classically a restrictive filling pattern. In addition, left atrial enlargement and mitral valve insufficiency are common. These cats are also at risk for thrombus formation and thromboembolic events.

The most effective therapy for this disorder remains unknown.  The underlying disorder is that of diastolic dysfunction.   ACE inhibitor therapy is used if contractility is reduced. Furosemide is used in the presence of CHF. These patients are at risk for thromboembolic events, hence prophylaxis is warranted.

The prognosis is unknown but generally very poor.

We have observed a few cats with a form of end stage myocardial failure that is characterized by left ventricular enlargement, reduced contractility, focal regions of myocardial hypokinesis or akinesis with marked thinning of the wall in these akinetic/hypokinetic areas (usually the left ventricular free wall at the base), enlargement of the right ventricle and atrium, reduced contractility of the right atrium, and left atrial enlargement.

It appears that myocardial infarction and ischemia play a major role in producing the overall morphologic changes observed.

One wonders if these cats are in the final stages of a progressed version of one of the other more classical forms of cardiomyopathy.

Management is attempted as for the restrictive form of CM.

Prognosis is usually abysmal with death within 2 weeks.

Feline hyperthyroidism is a disorder of older cats (>6 years) associated with the overproduction of thyroid hormone.  The tumour itself is relatively innocuous but the systemic effects of the overproduction of thyroid hormone cause the signs of disease.

a) Signalment:

• > 6 yrs of age cat
• Any breed

b) History:

• Weight loss - 96%
• Polyphagia - 77%
• Hyperactivity - 68%
• Polydipsia/polyuria - 53%
• Vomiting - 49%
• Diarrhea - 31%
• Increased fecal volume 28%
• Panting - 28%
• Muscle weakness - 22%
• Muscle tremor - 14%
• Signs of congestive heart failure - 13%
• Dyspnea - 13%

Comments:  About 10% of cats do not show hyperexcitability or restlessness but manifest with extreme depression and weakness as the primary complaint.

c) Physical Examination - may reveal:

• Emaciation
• Palpable thyroid mass - 85 to 90% of cases
• Tachycardia
• Dysrhythmias, pulse deficits
• Gallop rhythm
• Heart murmur (AV valve insufficiency)
• Dyspnea
• Signs of congestive heart failure

Feline hyperthyroidism is definitively diagnosed with the demonstration of an elevated serum T4 level.

a) Radiology:

• Radiology is useful to detect complications associated with thyrotoxicosis
• The pattern may be suggestive of hypertrophic cardiomyopathy
• Pulmonary venous congestion
• Pulmonary edema
• Pleural effusion
• Cardiomegaly
• There are no definitive findings indicative of hyperthyroidism

b) ECG - may reveal

• Normal ECG
• Increased R wave amplitude
• Sinus tachycardia
• Premature beats (atrial or ventricular)
• Widened QRS complexes
• No findings are definitive of hyperthyroidism

c) Blood Work - may reveal:

• Note that the serum T4 level can vary from sample to sample therefore if one is suspicious several T4 samples should be taken
• At times the total T4 may be normal but the free T4 will be elevated in hyperthyroidism
• A T3 suppression test demonstrating a flat response may provide a definitive diagnosis when the T4 level is normal
• A TSH stimulation test demonstrating a flat response supports a diagnosis of hyperthyroidism
• Elevated liver enzymes particularly ALT, AST, alkaline phosphatase
• In that these are old cats, other concurrent abnormalities may be present esp. renal disease
• Usually hypertensive

d) Echocardiography:

• Many cases of hyperthyroidism have findings typical of feline HCM
• A few cases have findings somewhat intermediate between those of feline HCM and feline DCM
• Infrequently one observes findings typical of feline DCM

Comment:  The reports of hyperthyroidism that occurred in association with feline dilated cardiomyopathy were documented in the pre-taurine supplementation days.  It is entirely possible that these cases also represented taurine deficiency.

e) Thyroid Imaging (radioisotope):

• 70% of hyperthyroid cats: both lobes appear enlarged
• 30% of hyperthyroid cats: only one lobe is enlarged and the contralateral lobe is suppressed and not visible
• Imaging can identify intrathoracic thyroid tissue in hyperthyroid cats
• Imaging can detect regional or distant metastasis of functional thyroid carcinoma

Therapeutic Goals:

1. Control the cardiac manifestation of hyperthyroidism which occurs a result of excessive sympathetic stimulation.

1. If the echocardiographic picture is one of concentric hypertrophy, treat as per feline hypertrophic cardiomyopathy
2. If the echocardiographic picture is one of eccentric hypertrophy, treat as per feline dilated cardiomyopathy
3. If dysrhythmias are present (premature beats):
• Beta blockers tend to be the general class of antidysrhythmics of choice. They may also be effective if sinus tachycardia is present.
• Propranolol: 0.2 - 1 mg/kg BID-TID (PO)
• Metoprolol:  5-15 mg TID (PO)
• Atenolol:  5-12.5mg SID-BID (PO)
• Propranolol has drawbacks in its combined beta 1 and beta 2 blocking activity (promotes bronchoconstriction, this is particularly worrisome if pulmonary edema is present). The selective beta blockers metoprolol and atenolol are preferable in patients with respiratory distress.
4. Antithyroid medication - to reduce the systemic effects of hyperthyroidism:
• Methimazole - 5 mg BID-TID (PO)

On this therapy, most cats become euthyroid in 2 to 3 weeks.  If little or no decrease in serum T4 levels occurs on this dosage regimen, dosages of methimazole should be increased to 7 to 10 mg TID (PO).

5. Surgical excision of thyroid tumors results in long term cure.  Surgical procedures must attempt to preserve at least 1 parathyroid gland.  Schedule surgery when cat is euthyroid.

6. Radioactive Iodine:

• Simple, effective, and safe
• Radioactive iodine is concentrated primarily in the hyperplastic or neoplastic thyroid cells irradiating and destroying the hyperfunctioning tissue.
• Normal thyroid tissue is protected from the effects of radio active iodine since the uninvolved thyroid tissue is suppressed and receives only a small dose of radiation
• Requires a nuclear facility

Comments: Adverse drug reactions

1. General signs:
   • Anorexia, vomiting, and lethargy. These signs are transient and usually resolve despite continued drug therapy
   • Adverse GI signs may persist --> stop drug
2. Increased renal parameters reflecting reduced GFR – subclinical renal disease may be unmasked.
3. Granulocytopenia may occur with methimazole. CBCs must be monitored.
4. If adverse effects occur, recommend treat with beta blocker alone (use with caution if feline DCM or intermediate CM is present).

Comments:  Site of tumour

Because the thyroid lobes of the cat are loosely attached to the trachea, the enlarged lobe(s) frequently descend ventrally from its normal location adjacent to the larynx.  Many cats in which a thyroid mass is not palpable have tumorous lobes that have descended into the thoracic cavity. 70% of cases have bilateral thyroid lobe involvement.  30% of cases have single thyroid lobe involvement.  Of those cases with true unilateral lobe involvement, recurrence in the contralateral lobe is unusual.  Of those cases with bilateral lobe involvement, about 15% of these have one lobe that is minimally enlarged and is usually mistaken as normal.  Therefore if only one lobe is removed, relapse of hyperthyroidism will usually occur within 9 months of surgery.  Preservation of the external parathyroid gland during hemithyroidectomy minimizes the risk of hypoparathyroidism should removal of the contralateral lobe be required.  It can be difficult to remove all abnormal thyroid tissue while attempting to concurrently preserve parathyroid tissue.  Small remnants of thyroid tissue that remain attached to the parathyroid may regenerate and produce thyrotoxicosis in 6 to 12 months.  Hypocalcemia is the most important complication associated with bilateral thyroidectomy.  It doesn't occur with unilateral thyroidectomy.  After bilateral thyroidectomy, the serum calcium concentration should be monitored on a daily basis until it has stabilized within the normal range.  After bilateral thyroidectomy hypocalcemia will develop in 1 to 3 days if it is to occur.  Although hypocalcemia may be permanent in some cats, spontaneous recovery of parathyroid function may occur weeks to months after surgery.  In most cases, such transient hypocalcemia results from reversible parathyroid damage and ischemia secondary to surgery.  Alternatively, accessory parathyroid tissue may compensate for the damaged parathyroid glands and maintain normocalcemia.

Prognosis will vary depending on

a) If the echocardiographic features are those of feline dilated cardiomyopathy:

• the prognosis is very poor

b) If the echocardiographic features are those of feline hypertrophic cardiomyopathy:

• the prognosis for complete recovery with surgical excision or radioactive iodine therapy is excellent

Comment:  Recall that most of these cats are quite old and therefore are subject to a number of geriatric disorder including:  chronic renal disease, and hepatic disease which may render them poor anesthetic risks.  Many cats can be controlled long term with chronic anti-thyroid therapy if adverse blood disorders do not occur.

1. Some General Statements:

Boxer cardiomyopathy is a disorder characterized primarily by ventricular arrhythmias, syncope, and sudden death. LV systolic dysfunction and CHF, the typical characteristics of canine dilated cardiomyopathy, are relatively rare in Boxer cardiomyopathy. Boxer cardiomyopathy closely resembles an arrhythmic disorder in humans called Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), and as such, the name ARVC is now used to refer to the arrhythmic cardiomyopathy of Boxers. (Boxers in the UK appear to be much more commonly affected with the DCM form of the disease).

2. Etiology of Boxer cardiomyopathy (ARVC):

ARVC is a familial disease in Boxers that is inherited as an autosomal dominant trait with variable penetrance.
An 8 base pair deletion on chromosome 17 located within the striatin gene was found to be associated with affected Boxers and absent in normal Boxers and normal other dogs (Meurs et al. JVIM 2009;23:687-688).
A disorder of carnitine metabolism is involved in a few cases of the relatively uncommon form of Boxer cardiomyopathy with LV failure and CHF.

3. Signalment:

• Age range = 1 - 15 years
• Most cases (60%) are 6 to 10 years of age

4. History:

Based on clinical signs, three categories can be defined:

1. Dogs with no clinical signs of heart disease.
2. Dogs with syncope or weakness.
3. Dogs with signs of left-sided congestive heart failure.

5. Clinical Signs:

• May be free of clinical signs
• May have syncope or episodic weakness
• aA small percentage (<10%) have cough and/or dyspnea

6. Physical Examination:

• Many have a normal physical exam
• Cardiac arrhythmias may be ausculted
• Pulse deficits may be present with dysrhythmias
• Very few have a murmur of mitral valve insufficiency

7. ECG:

The ECG provides the most consistent findings.

1. Ventricular premature beats are common, and may occur

• as single beats
• as pairs or triplets
• in runs of ventricular tachycardia

Most ventricular premature beats are of right ventricular origin (QRS is upright in lead II).
Sometimes the ventricular premature beats are multiform.
While the exact number of VPCs above which a dog should be considered affected is unknown, the observation of >100 VPC's/24 hours is highly suspicious, and periods of couplets, triplets, or runs of ventricular tachycardia are generally considered abnormal.

Note: Since the arrhythmias are intermittent, a normal routine (i.e. 2-minute) ECG does NOT rule out the disease, thus it can be a very poor screening test. A 24-hour Holter monitor is much more useful for screening, and is also recommended to evaluate the quantity and complexity of arrhythmia in a Boxer that does exhibit ventricular arrhythmias on routine ECG.

2. Supraventricular arrhythmias are much less common, and are typically associated with the uncommon myocardial dysfunction form of the disease:

• Supraventricular premature beats
• Aupraventricular tachycardia
• Atrial fibrillation

8. Radiography:

• Normal findings are most common
• General cardiomegaly with mild to moderate left atrial enlargement, pulmonary venous congestion, and pulmonary edema are seen in the uncommon form with LV systolic dysfunction

9. Echocardiography:

• The majority of affected Boxers have a normal echocardiogram
• A small percentage (~7%) have evidence of left ventricular dilation and hypokinesis (systolic dysfunction)

10. Therapy:

1. Cases free of clinical signs:

The criteria for initiating therapy in asymptomatic dogs remain ill-defined, and depend not only on the absolute number of VPCs observed but also on the complexity of the arrhythmia. Antiarrhythmic therapy is generally indicated if:

Frequent premature beats are present (certainly if >1000 VPC's/24 hours on a Holter monitor, and potentially if >500/24 hours)

There are runs of ventricular tachycardia

The VPCs exhibit a very short coupling interval (R-on-T phenomenon)

Based on work by Dr. K. Meurs et al, the most efficacious antiarrhythmics for Boxers with ARVC are:

1. Sotalol: 1.5-3.5 mg/kg BID (PO)

2. Combination of mexiletine and atenolol
   mexiletine: 5-8 mg/kg TID (PO)
   atenolol: 0.3-0.6 mg/kg or 12.5 mg/DOG BID (PO)

2. Syncopal/weakness cases:  secondary to ventricular dysrhythmias but unassociated with signs of heart failure.

• Antidysrhythmic therapy can be instituted as described per asymptomatic cases
• In acute situations, procainamide or lidocaine may be used:

Procainamide 6-8 mg/kg (IV) over 5 min, then 25 to 30 ug/kg/min CRI for 3 hours

Lidocaine 2 mg/kg IV bolus, then 25 to 75 ug/kg/min

3. Cases with congestive heart failure and cardiac dysrhythmias:

Goals of therapy include:
1. Management of heart failure as per question 16 in General Therapeutic Concepts section
• Should include supplementation with carnitine 50 mg/kg BID-TID (PO)
2. Management of cardiac dysrhythmias.
1. Supraventricular dysrhythmias including atrial fibrillation are managed as per Electrocardiology section
2. Ventricular dysrhythmias are managed as per above
11. Prognosis:

It is important to recognize that sudden death is always possible. While the goal of antiarrhythmic therapy is to reduce this risk, sudden death is still possible in the face of antiarrhythmics.

1. Asymptomatic dogs may live for several years without clinical signs

2. Cardiac dysrhythmias with syncope but without heart failure:

• With antiarrhythmic therapy syncope can usually be dramatically reduced and most dogs survive for several to many years
• If they develop CHF their prognosis falls dramatically

3. Congestive heart failure with cardiac dysrhythmias

• Usually fail to survive for more than 6 months

There have been very few reports of idiopathic hypertrophic cardiomyopathy in the dog. Most cases of left ventricular concentric hypertrophy are due to systemic hypertension and aortic stenosis (usually subaortic stenosis). Dr. Charla Jones has suggested that idiopathic hypertrophic cardiomyopathy may be common in the Golden Retriever. Dr. David Sisson has reported familial HCM in a line of pointer dogs. We have also observed HCM in several pointer dogs, Golden Retrievers, German Shepherds, Rottweilers, and Jack Russell Terriers. The significance of this disorder remains to be determined in the dog.

1. Congenital pericardial disorders

• Peritoneal-pericardial diaphragmatic hernia
• Pericardial defects
• Pericardial cysts

2. Acquired pericardial disorders

1. Pericardial effusion

• Transudate or modified transudate (hydropericardium)
• Congestive heart failure (increased hydrostatic   pressure)
• Hypoalbuminemia (reduced oncotic pressure)
• Exudate (pericarditis)
• Septic (bacterial, fungal)
• Sterile (idiopathic, uremic, immune)
• Hemorrhagic (hemopericardium)
• Neoplastic (hemangiosarcoma, heart base tumor, lymphosarcoma, mesothelioma)
• Traumatic
• Left atrial rupture
• Coagulopathy
• Idiopathic

2. Constrictive pericarditis

• Neoplasia
• Infection (bacterial, fungal)
• Idiopathic
• Pericardial foreign body

3. Pericardial mass lesion (with or without effusion or fibrosis)

• Pericardial cyst
• Granuloma (fungal infections)
• Neoplasia

Of all the causes of pericardial disease, the development of pericardial effusion is the most frequent pathogenic process or consequence of the pericardial disorder.  The clinical signs of the pericardial disorder are thus a consequence of the pericardial effusion.

Pericardial effusion is the disorder characterized by the accumulation of fluid (serous, blood, chyle, pus) within the pericardial sac.  As fluid collects it markedly impedes the filling ability of the heart (diastolic dysfunction).  The right side of the heart tends to "suffer" most with this diastolic dysfunction.

Pericardial effusion may develop relatively slowly or may develop rapidly.  If the fluid accumulates rapidly, right heart dysfunction occurs rapidly.  If the fluid accumulates gradually, the pericardium can stretch to accommodate a great volume of fluid with minimal cardiac impairment.

Etiology: The idiopathic and neoplastic etiologies are by far the most common in the dog.  Hemangiosarcoma (HSA) is the main tumor. Heart base tumor is another (most commonly chemodectoma or ectopic thyroid carcinoma). The disorder is uncommon in cats.  The neoplastic (HSA) cause is the most common of all causes.

1. Signalment:

1. Breeds - large breed dogs more commonly affected with both etiologies (German Shepherd and G. Shepherd crosses are most commonly affected with hemangiosarcoma)

2. Age - middle aged and older

2. History:

• Sudden weakness
• Exercise intolerance
• Increased respiratory effort

3. Physical Examination:

• The triad of muffled heart sounds, jugular venous distention, and weakened arterial pulses is diagnostic of pericardial effusion
• Signs of right heart failure

The diagnostic test of choice is echocardiography.

A presumptive diagnosis can be made with:

1. A large globose heart on radiography and
2. The Triad of jugular venous distention, muffled heart sounds, and weak arterial pulse detected on physical examination.

1. Radiology:

• A very large globose heart (loss of chamber contour)
• Pulmonary edema is very unusual
• Pleural effusions are common. When present these can markedly obscure the silhouette of the heart thus “hiding” the radiographic appearance of a globose heart.
• Pulmonary metastatic lesions may be present (HSA)
• In the cat with hypertrophic cardiomyopathy we have seen both pleural effusion and pericardial effusion

2. ECG may show:

• Low amplitude QRS complexes
• Electrical alternans
• Usually normal (sinus rhythm)
• Sinus tachycardia
• Ventricular premature beats are common

3. Blood Work may show:

• CBC evidence of hemangiosarcoma may be present (nucleated rbc, regeneration, schistocytes, with a fairly normal PCV)

4. Echocardiography:

• Pericardial effusion is readily detected
• A tumor present in the region of the right auricle, right atrium, or right ventricle in cases of hemangiosarcoma
• A tumor at the base of the aorta (heart base tumor) may be noted
• Cardiac tumors are easier to visualize while the effusion is still present

5. Other tests:

• Cytology of pericardial fluid.
  • This analysis has been shown to be of little value in distinguishing between idiopathic and neoplastic etiologies. However, the pericardial fluid analysis may reveal a septic etiology or the presence of chyle

• Pneumopericardiography:
  • At the time of centesis, a volume of carbon dioxide equal to 1/2 to 3/4 the volume of fluid removed from the pericardial sac is injected into the sac followed by both lateral radiographic views and a D/V and V/D view. This procedure has been useful to identify the presence of heart base tumors. The availability of cardiac ultrasound makes pneumopericardiography much less useful.

Cardiac tamponade refers to the condition whereby the pericardial effusion has caused a significant reduction in right ventricular function such that heart failure has resulted.  Thus cardiac tamponade represents the most severe form or consequence of pericardial effusion.  On physical examination the arterial pulses are markedly reduced, the heart sounds are muffled, and there is jugular venous distention.  On history there is evidence of weakness, exercise intolerance, or syncope.

The presence of cardiac tamponade represents a cardiac emergency and requires immediate attention.  Immediate pericardiocentesis is indicated.

Goals of Therapy:

1. To quickly control the distensibility abnormality especially if cardiac tamponade is present:
   • Pericardiocentesis
2. To control recurrent episodes of effusions:
   • Repeated pericardiocentesis as pericardial effusion recurs
   • Corticosteroids may retard/prevent recurrence in idiopathic cases (prednisone: 0.5 mg/kg BID (PO))
   • Surgical removal of the pericardial sac

Comments:

• Surgery not only allows for removal of the pericardial sac but also for the determination of an underlying neoplastic process.
• Pericardiocentesis is not a benign procedure. The risk of coronary artery laceration is substantial if done improperly which could result in sudden death. When performed, the procedure should enter the pericardial sac from the right hemithorax. Also an ECG should be performed simultaneously to detect epicardial irritation/contact.
• In contrast to the literature, the author believes the neoplastic etiologies are more common than the idiopathic variety.
• In cases of hemangiosarcoma, metastasis has usually occurred by the time the right auricular mass is detected.

• With idiopathic pericardial effusions, the long term prognosis is excellent if the pericardial sac is removed.  Without a pericardectomy, several repeated pericardiocentesis procedures may be required.
  
• With neoplastic induced pericardial effusion, the long term prognosis is very poor.  Repeated pericardial effusion is the rule, although pericardectomy can be palliative.  Animals usually die of this disorder within 6 months.

1. Definition:
   Pericardial disease characterized by fibrosis of the pericardium (usually only the parietal pericardium). Usually pericardial fibrosis exists without concurrent pericardial effusion.

2. Consequence:
   Pericardial fibrosis causes a restriction to the filling of the right ventricle (just like pericardial effusion). As right ventricular filling (diastolic dysfunction) is reduced cardiac output falls and right heart preload increases.

3. Presenting signs:
   As with cardiac tamponade, dogs present for weakness, exercise intolerance, syncope, abdominal enlargement, dyspnea. Although this disorder can occur a result of previous pericardial disease, most dogs have no history of prior pericardial or cardiovascular disease.

4. Signalment:
   Middle aged dogs, both sexes equally represented, mainly in large breeds.

5. Physical examination findings:
   Most of the signs are very similar to pericardial effusion, this is not surprising since both result from right heart failure. Signs include jugular venous distention, hepatomegaly, and ascites. The heart sounds are usually muffled, arterial pulses are weak, and gallop heart sounds are rare.

6. ECG findings:
   - Low amplitude QRS in 50 %
   - Prolonged P wave duration - frequent
   - Sinus rhythm - typical, often sinus tachycardia
   - Atrial fibrillation - infrequent

7. Radiographic findings:
   - Absence of a globose heart
   - Variable amount of pleural effusion, although usually absent
   - Mild to moderate cardiomegaly
   - Caudal vena caval enlargement
   - No pulmonary edema

8. Echocardiographic findings:
   - Absence or minimal pericardial effusion
   - Difficult or impossible to determine that the pericardium is thickened

9. Presumptive diagnosis:
   Very difficult to make a presumptive diagnosis. Often a default diagnosis for an individual with signs of right heart failure (jugular venous distention, ascites, pleural effusion). Constrictive pericarditis is considered after other causes of right heart failure such as congenital, valvular, myocardial, and respiratory disease (cor pulmonale), heartworm, and pericardial effusion have been excluded.

10. Definitive diagnosis:
    Cardiac catheterization will demonstrate elevation of pressures and simultaneous equalization of left and right atrial and ventricular pressures.
    Surgical demonstration of pericardial fibrosis and resolution of signs with pericardectomy.

11. Therapy:
    Subtotal parietal pericardectomy usually without epicardial stripping.

12. Prognosis:
    Response to surgery is usually excellent. Recurrence may be a concern.

• Most cases of pericardial effusion in the cat occur secondary to heart failure and likely contribute minimally to the hemodynamic incompetence.
• Pericardial disease is not commonly diagnosed antemortem
• Of clinically significant pericardial disease in the cat, neoplastic and infectious causes are reportedly most important.
• We have seen a number of cats demonstrate pericardial effusion secondary to HCM

Bacterial endocarditis is usually a multisystemic disorder associated with bacteremia and the infection of joints, kidneys, and cardiac valves.

The joint disease may be of two types:

1. Septic joint disease or
2. Immunologic joint disease

The renal disease may result in acute renal failure due to diffuse ischemia or may be occult.

The cardiac disease may cause any of the following:

1. Dysrhythmias
   - premature beats/tachycardia
   - heart block
2. Destruction of the mitral valve leaflets may cause severe mitral valve insufficiency with left ventricular volume overload.
3. Rupture of a chordae tendinae may result in massive mitral valve insufficiency and fulminant pulmonary edema and death.
4. Destruction of the aortic valve with severe aortic insufficiency. This results in severe LV volume overload, congestive heart failure and death.

1. Signalment:

1. Breeds -

• Dogs with congenital subaortic stenosis
• Large breed dogs are more commonly affected. German Shepherds are the most common breed affected overall.

2. Age -  middle age or older (ave. = 5 yrs)
3. Sex - primarily in males

2. History may include:

• Anorexia, lethargy, depression
• Vomiting
• Lameness
• Heart failure/congestive heart failure

3. Physical examination:

• A new heart murmur of mitral valve insufficiency or
• Aortic valve insufficiency, previously undetected
• Exuberant arterial pulses occur when aortic insufficiency develops
• Dysrhythmias
• Fever
• Joint pain, swelling, heat
• Pale mucous membranes
• Dyspnea
• Congestive heart failure

Comment:  The clinical signs of bacterial endocarditis are related to:

• Cardiac lesions
• Arterial emboli
• Host response to infection

The definitive diagnosis for bacterial endocarditis can be obtained by:

1. Echocardiographic evidence of vegetative valvular endocarditis along with a positive blood culture.

A presumptive diagnosis of bacterial endocarditis can be made by:

1. The development of a new heart murmur.
2. Evidence of septic or immune joint disease.
3. A positive blood culture.

Results of diagnostic tests:

1. Radiology:

• Will likely be normal
• There may be marked LAE and/or LVE
• Evidence of heart failure would be unusual unless aortic valve insufficiency is present or a ruptured chordae tendinae results in fulminate mitral valve insufficiency.

2. ECG may show:

• Ventricular ectopy
• Heart block
• Aberrant conduction

3. Blood Work may show:

• Positive blood culture in 1/3 of cases
• Leukocytosis with left shift and toxic changes
• May see evidence of kidney disease

4. Echocardiography may show:

• Vegetative lesion on the mitral valve and/or aortic valve
• Mitral regurgitation
• Aortic valve regurgitation
• There may be marked LAE and/or LVE

5. Other tests:

• Positive blood culture - 81%
• Positive urine culture
• Immune joint aspirate cytology
• Septic joint

Comment:

1. Aortic valve regurgitation or mitral valve regurgitation can occur due to destruction and perforation of valve leaflets.
2. Valvular disease can result in cardiac dysfunction and heart failure
3. Septic emboli can result in:
   - myocarditis
   - glomerulonephritis
   - arthritis

Goals of therapy:

1. Antimicrobial therapy:
   The most common bacteria are Staphylococci, Streptococci, and E. coli. Bartonella spp. have been identified in culture negative cass. Therapy should be based on culture and susceptibility where possible. The empiric antibiotics of choice for broad-spectrum coverage are penicillins or cephalosporins combined with fluoroquinolones or aminoglycosides for 5-6 weeks.
2. Provide fluid and caloric support where appropriate.
3. Treat heart failure if it develops.

Comment: A high serum concentration of antibiotic and prolonged duration of therapy are necessary because of the difficulty in reaching bacteria within the vegetative lesion of platelets and fibrin.  Bactericidal antibiotics are indicated because the host's phagocytic cells cannot always reach the infective organisms.

The prognosis for cases of bacterial endocarditis is poor (50% die). If heart failure develops, the prognosis is grave.