Myocardial Disease: Canine- Ettinger

Question 1

CANINE DILATED CARDIOMYOPATHY

Dilated cardiomyopathy (DCM) is a primary myocardial disease characterized by cardiac enlargement and impaired …………… function of one or both ventricles (Figure 251-1). ………………. dysfunction may also be observed.[2]

Answer 1

CANINE DILATED CARDIOMYOPATHY

Dilated cardiomyopathy (DCM) is a primary myocardial disease characterized by cardiac enlargement and impaired systolic function of one or both ventricles (Figure 251-1). Diastolic dysfunction may also be observed.[2]

Question 2

An increased understanding of the etiology of both the human and canine disease has led to the development of the theory that DCM is the final result of a variety of myocardial insults including viral, nutritional, toxic, and genetic.3 In human beings, the disease has been shown to be familial in at least 20% to 40% of the cases and causative mutations have been identified in 24 genes.[4] The etiology in many cases is never determined and they are considered idiopathic.

Answer 2

An increased understanding of the etiology of both the human and canine disease has led to the development of the theory that DCM is the final result of a variety of myocardial insults including viral, nutritional, toxic, and genetic.3 In human beings, the disease has been shown to be familial in at least 20% to 40% of the cases and causative mutations have been identified in 24 genes.[4] The etiology in many cases is never determined and they are considered idiopathic.

Surveys in North American publications find an increased incidence in the Doberman Pinscher, Irish Wolfhound, Great Dane, and Cocker Spaniel.[12],[13] European sources suggest an increased incidence of the Airedale Terrier, Doberman Pinscher, Newfoundland, and English Cocker Spaniel.[14] The differences in breed prevalence between the canine populations may suggest an influence of environmental factors on the development of DCM but are more likely related to the strong genetic influences of certain popular dogs within an area.

Question 3

DCM is an adult-onset disease, with the exception of the Portuguese Water Dog, in which it is diagnosed between 2 and 32 weeks

Answer 3

DCM is an adult-onset disease, with the exception of the Portuguese Water Dog, in which it is diagnosed between 2 and 32 weeks

Question 4

PHYSICAL EXAMINATION

A soft systolic murmur consistent with mitral valve regurgitation and/or a gallop rhythm (S3) may be auscultated at the left apex. A tachyarrhythmia of ventricular or atrial origin may be noted. In some cases, these may be the first signs of the occult form of the disease and should not be overlooked.

Answer 4

PHYSICAL EXAMINATION

A soft systolic murmur consistent with mitral valve regurgitation and/or a gallop rhythm (S3) may be auscultated at the left apex. A tachyarrhythmia of ventricular or atrial origin may be noted. In some cases, these may be the first signs of the occult form of the disease and should not be overlooked.

Question 5

Echo: In some cases, the ventricular wall thickness may appear thin during diastole, but generally when it is measured it is found to be within normal limits.

An important part of the diagnosis is usually concurrent left ventricular ……………. dysfunction based upon decreased fractional shortening (FS%), ejection fraction (EF%) or shortening area, and increased end-……………. volume. Many dogs may demonstrate ……….. dysfunction as well, as determined by evaluation of transmitral flow and pulmonary venous flow. Doppler echocardiography may be used to document a central jet of mitral regurgitation that may be associated with dilation of the ventricle.

Answer 5

In some cases, the ventricular wall thickness may appear thin during diastole, but generally when it is measured it is found to be within normal limits.

An important part of the diagnosis is usually concurrent left ventricular systolic dysfunction based upon decreased fractional shortening (FS%), ejection fraction (EF%) or shortening area, and increased end-systolic volume. Many dogs may demonstrate diastolic dysfunction as well, as determined by evaluation of transmitral flow and pulmonary venous flow.[2] Doppler echocardiography may be used to document a central jet of mitral regurgitation that may be associated with dilation of the ventricle.

Question 6

A differential diagnosis for DCM is severe atrioventricular (AV) valve disease because severe ventricular dilation and systolic dysfunction may be occasionally observed in these cases. Consideration of the breed of dog may be helpful in differentiating between DCM and AV valve disease because it is uncommon for many of the large breed dogs to develop significant primary valve disease. An exception to this may be the Cocker Spaniel, a breed that has a high incidence of primary valve disease and is also at increased risk of DCM

Answer 6

A differential diagnosis for DCM is severe atrioventricular (AV) valve disease because severe ventricular dilation and systolic dysfunction may be occasionally observed in these cases. Consideration of the breed of dog may be helpful in differentiating between DCM and AV valve disease because it is uncommon for many of the large breed dogs to develop significant primary valve disease. An exception to this may be the Cocker Spaniel, a breed that has a high incidence of primary valve disease and is also at increased risk of DCM

Question 7

Unfortunately, the diagnosis of the occult stage of DCM is much more difficult. In some cases, dilation of the ventricle precedes the development of systolic dysfunction and is an early indicator of DCM. However, this is not always the case and systolic dysfunction may precede dilation.

Answer 7

Unfortunately, the diagnosis of the occult stage of DCM is much more difficult. In some cases, dilation of the ventricle precedes the development of systolic dysfunction and is an early indicator of DCM.[15] However, this is not always the case and systolic dysfunction may precede dilation.

Question 8

Annual two-dimensional and M-mode echocardiography is recommended for adult dogs of at-risk breeds or if early signs (heart murmur, gallop, tachyarrhythmias) are detected. Additional studies that have been suggested for additive information when evaluating borderline cases include measurement of the mitral valve annulus motion, systolic time intervals, systolic and diastolic performance index, and stress echocardiography.

Answer 8

Annual two-dimensional and M-mode echocardiography is recommended for adult dogs of at-risk breeds or if early signs (heart murmur, gallop, tachyarrhythmias) are detected. Additional studies that have been suggested for additive information when evaluating borderline cases include measurement of the mitral valve annulus motion, systolic time intervals, systolic and diastolic performance index, and stress echocardiography.

Question 9

PATHOLOGY

Gross pathology of DCM typically demonstrates dilation of both the left and right atria and ventricles, although in some cases, the left side is more affected than the right.[25-27] Myocardial eccentric hypertrophy should also be evident by an increased heart-to–body weight ratio.
Histopathologic findings may vary and are generally fairly nonspecific. Common findings can include ……………….

Answer 9

PATHOLOGY

Gross pathology of DCM typically demonstrates dilation of both the left and right atria and ventricles, although in some cases, the left side is more affected than the right.[25-27] Myocardial eccentric hypertrophy should also be evident by an increased heart-to–body weight ratio.
Histopathologic findings may vary and are generally fairly nonspecific. Common findings can include attenuated wavy myofibers, fibrosis, vacuolization of myocytes, necrosis, and in some cases fatty infiltration.

Question 10

ETIOLOGY

The term cardiomyopathy can be used to define myocardial diseases caused by a variety of factors including genetic, viral, and nutritional.[3] In many canine cases, the cause is unknown. It is clear that several breeds appear to be overrepresented, and some breeds seem to have unique characteristics of the disease that may suggest this is a unique disease for their breed. A familial form of DCM has now been identified in several breeds and is suspected in others. Occasionally, atypical breeds of dogs develop DCM. The etiology of the disease in these cases is unknown and external factors that can insult the myocardium including infectious organisms or nutritional imbalances should be considered.

Answer 10

The term cardiomyopathy can be used to define myocardial diseases caused by a variety of factors including genetic, viral, and nutritional.[3] In many canine cases, the cause is unknown. It is clear that several breeds appear to be overrepresented, and some breeds seem to have unique characteristics of the disease that may suggest this is a unique disease for their breed. A familial form of DCM has now been identified in several breeds and is suspected in others.[8,28,29] Occasionally, atypical breeds of dogs develop DCM. The etiology of the disease in these cases is unknown and external factors that can insult the myocardium including infectious organisms or nutritional imbalances should be considered.

Question 11

Breed-Specific Dilated Cardiomyopathy

Cocker Spaniels

DCM has been reported in both American and English Cocker Spaniels.[1,5,37]An association between the development of DCM and low plasma taurine levels has been reported in some American Cocker Spaniels.[5] American Cocker Spaniels with low taurine levels that were provided taurine and L-carnitine supplementation showed an increase in FS% and a decrease in left ventricular end-diastolic and end-systolic diameter over a 4-month period, although myocardial function did not return to normal.[38] This study suggested that at least some American Cocker Spaniels with DCM may benefit from supplementation with taurine and, perhaps, L-carnitine.

Answer 11

DCM has been reported in both American and English Cocker Spaniels.[1,5,37]An association between the development of DCM and low plasma taurine levels has been reported in some American Cocker Spaniels.[5] American Cocker Spaniels with low taurine levels that were provided taurine and L-carnitine supplementation showed an increase in FS% and a decrease in left ventricular end-diastolic and end-systolic diameter over a 4-month period, although myocardial function did not return to normal.[38] This study suggested that at least some American Cocker Spaniels with DCM may benefit from supplementation with taurine and, perhaps, L-carnitine.

Question 12

Taurine levels may be assessed by evaluation of blood or plasma taurine levels, although blood levels are less affected by sample handling and recent feedings. American Cocker Spaniels with DCM should have blood or plasma levels of taurine measured and should be treated with 500 mg of taurine and 1.0 g of L-carnitine orally q 12 hours.[38] Additional treatment should be given as needed to address any other complications of the disease including CHF and arrhythmias. In many cases, supportive cardiovascular medications can be gradually withdrawn after the fractional shortening increases to at least 20% (usually after 3 to 4 months of supplementation). Supplementation with taurine, and L-carnitine if possible, should be continued for life.
In some cases of Cocker Spaniel DCM, taurine deficiency is not identified. The prognosis is generally poorer in these cases.

Answer 12

Taurine levels may be assessed by evaluation of blood or plasma taurine levels, although blood levels are less affected by sample handling and recent feedings. American Cocker Spaniels with DCM should have blood or plasma levels of taurine measured and should be treated with 500 mg of taurine and 1.0 g of L-carnitine orally q 12 hours.[38] Additional treatment should be given as needed to address any other complications of the disease including CHF and arrhythmias. In many cases, supportive cardiovascular medications can be gradually withdrawn after the fractional shortening increases to at least 20% (usually after 3 to 4 months of supplementation). Supplementation with taurine, and L-carnitine if possible, should be continued for life.
In some cases of Cocker Spaniel DCM, taurine deficiency is not identified. The prognosis is generally poorer in these cases.

Question 13

English Cocker Spaniels also get a form of DCM, but a relationship to taurine or carnitine levels has not been identified. Many reported dogs were from the same kennel, which may suggest a heritable component.[39],[40] Profound evidence of left ventricular enlargement on the electrocardiogram with R wave amplitudes >3.0 mV in lead II was frequently observed.[37] Some of the reported dogs died suddenly, but many have a prolonged, fairly asymptomatic course of disease, or a long survival (years) with medical management.[39]

Answer 13

English Cocker Spaniels also get a form of DCM, but a relationship to taurine or carnitine levels has not been identified. Many reported dogs were from the same kennel, which may suggest a heritable component.[39],[40] Profound evidence of left ventricular enlargement on the electrocardiogram with R wave amplitudes >3.0 mV in lead II was frequently observed.[37] Some of the reported dogs died suddenly, but many have a prolonged, fairly asymptomatic course of disease, or a long survival (years) with medical management.[39]

Question 14

Dalmatians

Dalmatians are occasionally diagnosed with DCM, although not as commonly as some of the other breeds including Doberman Pinschers, Great Danes, and Irish Wolfhounds.[1] Male dogs appear to be overrepresented in Dalmatian DCM, although large studies have not been performed.[6] 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 frequently 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 CHF. 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 low-protein diet may have resulted in an imbalance that could have led to the possible development of DCM; however, in the dogs that were tested, there was no evidence of L-carnitine or taurine deficiency. The cause and effect of these diets on the development of DCM is not known, but Dalmatians that develop DCM and 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.

Answer 14

Dalmatians

Dalmatians are occasionally diagnosed with DCM, although not as commonly as some of the other breeds including Doberman Pinschers, Great Danes, and Irish Wolfhounds.[1] Male dogs appear to be overrepresented in Dalmatian DCM, although large studies have not been performed.[6] 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 frequently 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 CHF. 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 low-protein diet may have resulted in an imbalance that could have led to the possible development of DCM; however, in the dogs that were tested, there was no evidence of L-carnitine or taurine deficiency. The cause and effect of these diets on the development of DCM is not known, but Dalmatians that develop DCM and 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.

Question 15

Doberman Pinschers

The Doberman Pinscher is one of the most commonly reported breeds of dogs to be diagnosed with DCM in North America.[7,13,41,45] It is an adult-onset disease that results in the development of left and/or biventricular failure, often with atrial fibrillation or sudden cardiac death.[42] The occult stage can be characterized by infrequent ventricular premature complexes (VPCs), mild ventricular dilation, and/or systolic dysfunction.[42] Diastolic function is often present.[2] The overt stage is often characterized by atrial fibrillation, VPCs, and CHF. Many affected dogs will first present for symptoms from their ventricular tachyarrhythmias including syncope and sudden cardiac death.[43],[44] Although syncope is often associated with the presence of ventricular tachyarrhythmias, bradycardia-associated episodic weakness and syncope have also been observed in cardiomyopathic Doberman Pinschers.[44] Therefore, every attempt should be made to determine the cause of the syncopal episodes with a Holter or event monitor before treatment is started.

Answer 15

The Doberman Pinscher is one of the most commonly reported breeds of dogs to be diagnosed with DCM in North America.[7,13,41,45] It is an adult-onset disease that results in the development of left and/or biventricular failure, often with atrial fibrillation or sudden cardiac death.[42] The occult stage can be characterized by infrequent ventricular premature complexes (VPCs), mild ventricular dilation, and/or systolic dysfunction.[42] Diastolic function is often present.[2] The overt stage is often characterized by atrial fibrillation, VPCs, and CHF. Many affected dogs will first present for symptoms from their ventricular tachyarrhythmias including syncope and sudden cardiac death.[43],[44] Although syncope is often associated with the presence of ventricular tachyarrhythmias, bradycardia-associated episodic weakness and syncope have also been observed in cardiomyopathic Doberman Pinschers.[44] Therefore, every attempt should be made to determine the cause of the syncopal episodes with a Holter or event monitor before treatment is started.

Question 16

Pathologic evaluation of the hearts of affected Doberman Pinschers identified a variety of nonspecific findings. Moderate to severe dilatation of all four cardiac chambers was often observed, although the left side was typically worse than the right. Heart weight to body weight ratios were often increased, ranging from 0.0008 to 0.0009 g/kg (normal 0.0007 ± 0.0003 g/kg).[29] Histologic lesions were characterized by marked myofiber degeneration and atrophy, myocardial replacement by thick bands of collagen fibers, interstitial fibrosis, aggregates of fat, multifocal myocytolysis, and myocardial necrosis.

Answer 16

Pathologic evaluation of the hearts of affected Doberman Pinschers identified a variety of nonspecific findings. Moderate to severe dilatation of all four cardiac chambers was often observed, although the left side was typically worse than the right. Heart weight to body weight ratios were often increased, ranging from 0.0008 to 0.0009 g/kg (normal 0.0007 ± 0.0003 g/kg).[29] Histologic lesions were characterized by marked myofiber degeneration and atrophy, myocardial replacement by thick bands of collagen fibers, interstitial fibrosis, aggregates of fat, multifocal myocytolysis, and myocardial necrosis.

Question 17

DCM in the Doberman Pinscher appears to be familial. An …………………… mode of inheritance has been defined by the appearance of the disease in multiple generations, equal gender representation, and evidence of male-to-male transmission[29] (Figure 251-3). Evidence that the disease is familial and the suggestion that early intervention may increase survival has led to significant interest in screening asymptomatic dogs for signs of occult disease.

Answer 17

DCM in the Doberman Pinscher appears to be familial. An autosomal dominant mode of inheritance has been defined by the appearance of the disease in multiple generations, equal gender representation, and evidence of male-to-male transmission[29] (Figure 251-3). Evidence that the disease is familial and the suggestion that early intervention may increase survival has led to significant interest in screening asymptomatic dogs for signs of occult disease.

Question 18

Annual echocardiography and ambulatory electrocardiography (Holter monitoring) are believed to be the best predictors of early DCM.[45],[46] Criteria that are believed to be indicators of occult disease include an echocardiographically determined left ventricular end-diastolic diameter greater than 4.6 cm and a left ventricular end-systolic diameter greater than 3.8 cm, even in the absence of systolic dysfunction.[17] These numbers are based on average-sized DCM dogs and may be less 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 (Figure 251-4).

Answer 18

Annual echocardiography and ambulatory electrocardiography (Holter monitoring) are believed to be the best predictors of early DCM.[45],[46] Criteria that are believed to be indicators of occult disease include an echocardiographically determined left ventricular end-diastolic diameter greater than 4.6 cm and a left ventricular end-systolic diameter greater than 3.8 cm, even in the absence of systolic dysfunction.[17] These numbers are based on average-sized DCM dogs and may be less 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 (Figure 251-4).

Question 19

Adult Doberman Pinschers with greater than 50 VPCs per 24 hours, or with couplets or triplets, are suspect for the development of DCM.[46] Measurement of BNP or NT-proBNP may also be useful for early detection of disease.[20] Owners should be advised that because this is an adult-onset disease with variability in the age of onset, screening tests should be performed annually.

Answer 19

Adult Doberman Pinschers with greater than 50 VPCs per 24 hours, or with couplets or triplets, are suspect for the development of DCM.[46] Measurement of BNP or NT-proBNP may also be useful for early detection of disease.[20] Owners should be advised that because this is an adult-onset disease with variability in the age of onset, screening tests should be performed annually.

Question 20

Great Danes

DCM in the Great Dane appears to be a familial disease.[8] In one study, affected …………..dogs were overrepresented, suggesting an X-linked pattern of inheritance in at least some families.[8] If this is true, ………. of affected females are at high risk of developing the disease; ………… of affected fathers are likely to be silent carriers.

Answer 20

Great Danes

DCM in the Great Dane appears to be a familial disease.[8] In one study, affected male dogs were overrepresented, suggesting an X-linked pattern of inheritance in at least some families.[8] 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.

Question 21

Affected Great Danes presented most commonly for weight loss and/or coughing. Left-sided heart murmurs, a gallop, and ascites were frequently observed. The most common electrocardiographic findings included atrial fibrillation with an occasional VPC. In some cases, atrial fibrillation developed before any other evidence of underlying myocardial disease (chamber enlargement or systolic dysfunction). Therefore, dogs with atrial fibrillation should be carefully evaluated for early DCM and should be followed annually for a few years to monitor for possible development of disease

Answer 21

Affected Great Danes presented most commonly for weight loss and/or coughing. Left-sided heart murmurs, a gallop, and ascites were frequently observed. The most common electrocardiographic findings included atrial fibrillation with an occasional VPC. In some cases, atrial fibrillation developed before any other evidence of underlying myocardial disease (chamber enlargement or systolic dysfunction). Therefore, dogs with atrial fibrillation should be carefully evaluated for early DCM and should be followed annually for a few years to monitor for possible development of disease.

Question 22

Irish Wolfhounds

DCM appears to be a familial trait in the Irish Wolfhound.[29],[47] The mode of inheritance is ………………with sex-specific alleles. Male dogs may be overrepresented.[9] As in the Great Dane, atrial fibrillation frequently preceded the development of a heart murmur, clinical signs, and CHF. Atrial fibrillation was present in the majority of Irish Wolfhounds by the time they developed DCM.[9],[48] The progression of the disease is not well understood but appears to be slow, with the development of atrial fibrillation preceding the development of CHF by an average of 24 months.[9] Occasionally, additional electrocardiographic abnormalities have been described including VPCs and left anterior fascicular block patterns. Affected Irish Wolfhounds occasionally died suddenly, but more commonly were euthanized due to heart failure, most commonly biventricular and sometimes with chylothorax

Answer 22

Irish Wolfhounds

DCM appears to be a familial trait in the Irish Wolfhound.[29],[47] The mode of inheritance is autosomal recessive with sex-specific alleles. Male dogs may be overrepresented.[9] As in the Great Dane, atrial fibrillation frequently preceded the development of a heart murmur, clinical signs, and CHF. Atrial fibrillation was present in the majority of Irish Wolfhounds by the time they developed DCM.[9],[48] The progression of the disease is not well understood but appears to be slow, with the development of atrial fibrillation preceding the development of CHF by an average of 24 months.[9] Occasionally, additional electrocardiographic abnormalities have been described including VPCs and left anterior fascicular block patterns. Affected Irish Wolfhounds occasionally died suddenly, but more commonly were euthanized due to heart failure, most commonly biventricular and sometimes with chylothorax

Question 23

Newfoundlands

Adult-onset DCM without a gender predisposition has been reported in the Newfoundland.[10],[18] Clinical presentation included dyspnea, cough, inappetence, and ascites with left or biventricular heart failure. Interestingly, a heart murmur was auscultable in only a very small percentage of the dogs (4/37).[10] The most common electrical abnormality was atrial fibrillation, but isolated VPCs were also observed.

Answer 23

Newfoundlands

Adult-onset DCM without a gender predisposition has been reported in the Newfoundland.[10],[18] Clinical presentation included dyspnea, cough, inappetence, and ascites with left or biventricular heart failure. Interestingly, a heart murmur was auscultable in only a very small percentage of the dogs (4/37).[10] The most common electrical abnormality was atrial fibrillation, but isolated VPCs were also observed.

Question 24

Portuguese Water Dogs

A juvenile form of familial DCM has been reported in the Portuguese Water Dog and is thought to be inherited as an ………………….. trait that is linked to a region on canine chromosome …….[11],[50] Affected puppies were from seemingly unaffected parents and typically died between 2 and 32 weeks of age, either from sudden collapse and death without any preceding signs or the development of CHF.[50]

Answer 24

Portuguese Water Dogs

A juvenile form of familial DCM has been reported in the Portuguese Water Dog and is thought to be inherited as an autosomal recessive trait that is linked to a region on canine chromosome 8.[11],[50] Affected puppies were from seemingly unaffected parents and typically died between 2 and 32 weeks of age, either from sudden collapse and death without any preceding signs or the development of CHF.

Question 25

Nutritional Cardiomyopathy Taurine-Related Cardiomyopathy The development of DCM due to low taurine is much less common in the dog than in the cat because......?

Answer 25

The development of DCM due to low taurine is much less common in the dog than in the cat because dogs have a much greater ability to synthesize taurine than cats. However, as mentioned earlier, a relationship between

Question 26

However, as mentioned earlier, a relationship between taurine and L-carnitine abnormalities and DCM has been previously described in the Cocker Spaniel.[5],[38] There have now been additional reports of the development of DCM in the dog in which low blood or plasma levels of taurine have been documented.[37] The dogs were all adult at the time of onset and were breeds that would be considered to be in the large-breed dog groups. A common factor observed in several dogs that developed DCM and were determined to have low taurine was the feeding of a diet of a dry dog food with lamb meal, rice, or both as the primary ingredient.[36] It has been hypothesized that rice bran or whole rice products may result in decreased taurine levels in some dogs. However, there is also a report of a family of Golden Retrievers with an apparent familial taurine deficiency and DCM. In a separate study of plasma taurine concentrations in dogs with heart disease, four out of six Golden Retrievers with DCM had low taurine levels.[34] These findings suggest that there may be some breed variations in taurine handling that could result in the development of DCM in certain breeds.

Answer 26

However, as mentioned earlier, a relationship between taurine and L-carnitine abnormalities and DCM has been previously described in the Cocker Spaniel.[5],[38] There have now been additional reports of the development of DCM in the dog in which low blood or plasma levels of taurine have been documented.[37] The dogs were all adult at the time of onset and were breeds that would be considered to be in the large-breed dog groups. A common factor observed in several dogs that developed DCM and were determined to have low taurine was the feeding of a diet of a dry dog food with lamb meal, rice, or both as the primary ingredient.[36] It has been hypothesized that rice bran or whole rice products may result in decreased taurine levels in some dogs. However, there is also a report of a family of Golden Retrievers with an apparent familial taurine deficiency and DCM. In a separate study of plasma taurine concentrations in dogs with heart disease, four out of six Golden Retrievers with DCM had low taurine levels.[34] These findings suggest that there may be some breed variations in taurine handling that could result in the development of DCM in certain breeds.

Question 27

A diagnosis of taurine deficiency is indicated by a blood level of less than 150 nmol/mL or plasma levels less than 40 nmol/mL. If taurine deficiency is suspected, taurine supplementation should be started while waiting for the results of the blood or plasma levels. Published doses for taurine supplementation appear to vary slightly, although 1000 mg/day (divided or once a day) appears to be a consistent recommendation.[35],[36] Additional cardiac medications should be provided as needed including inotropic support such as pimobenden and treatment of heart failure if needed. Taurine-deficient dogs with DCM appear to respond to supplementation fairly rapidly, and improvement in echocardiographic measurement should be observed in 3 to 6 months. Ideally blood levels of taurine should be reevaluated in 1 to 2 months to confirm that the levels have increased.

Answer 27

A diagnosis of taurine deficiency is indicated by a blood level of less than 150 nmol/mL or plasma levels less than 40 nmol/mL. If taurine deficiency is suspected, taurine supplementation should be started while waiting for the results of the blood or plasma levels. Published doses for taurine supplementation appear to vary slightly, although 1000 mg/day (divided or once a day) appears to be a consistent recommendation.[35],[36] Additional cardiac medications should be provided as needed including inotropic support such as pimobenden and treatment of heart failure if needed. Taurine-deficient dogs with DCM appear to respond to supplementation fairly rapidly, and improvement in echocardiographic measurement should be observed in 3 to 6 months. Ideally blood levels of taurine should be reevaluated in 1 to 2 months to confirm that the levels have increased.

Question 28

Treatment of the Dog with Dilated Cardiomyopathy The ideal treatment for DCM would be directed at the primary insult to the myocardium. Unfortunately, in the majority of cases, the underlying cause is not known and treatment should be directed to the identified cardiac abnormalities (e.g., systolic dysfunction, presence of heart failure or arrhythmias).

Answer 28

Treatment of the Dog with Dilated Cardiomyopathy The ideal treatment for DCM would be directed at the primary insult to the myocardium. Unfortunately, in the majority of cases, the underlying cause is not known and treatment should be directed to the identified cardiac abnormalities (e.g., systolic dysfunction, presence of heart failure or arrhythmias).

Question 29

Treatment of the Dog with Occult Dilated Cardiomyopathy Few studies have evaluated the benefit of medical therapy for dogs diagnosed in the occult stage of the disease; however, this area is likely to expand with our increasing ability to diagnose the disease early. Administration of angiotensin-converting enzyme (ACE) inhibitors may have some benefit for the dog with early ventricular dilation, with or without systolic dysfunction. The use of ACE inhibitors in the Doberman Pinscher with ventricular dilation was found to prolong the amount of time before the onset of CHF.[51] Although this study was limited to evaluation of Doberman Pinschers, the use of ACE inhibitors for other breeds of dogs with occult DCM may be considered.

Answer 29

Treatment of the Dog with Occult Dilated Cardiomyopathy Few studies have evaluated the benefit of medical therapy for dogs diagnosed in the occult stage of the disease; however, this area is likely to expand with our increasing ability to diagnose the disease early. Administration of angiotensin-converting enzyme (ACE) inhibitors may have some benefit for the dog with early ventricular dilation, with or without systolic dysfunction. The use of ACE inhibitors in the Doberman Pinscher with ventricular dilation was found to prolong the amount of time before the onset of CHF.[51] Although this study was limited to evaluation of Doberman Pinschers, the use of ACE inhibitors for other breeds of dogs with occult DCM may be considered.

Question 30

Administration of beta-blockers to the dog in the occult stage of DCM for a cardioprotective effect is still being evaluated. The addition of low-dose beta-blockers to the treatment of human patients with DCM and stable heart failure has demonstrated a reduction in both mortality and morbidity.[52] However, many human patients with DCM cannot tolerate even very low doses of beta-blockers and demonstrate rapid cardiac decompensation. One prospective, placebo-controlled canine study that looked at the effect of 3 months of the beta-blocker carvedilol at a gradually increasing dose did not identify any differences between the beta-blocker and placebo effect in echocardiographic indices of left ventricular size or function, neurohormonal activation, radiographic heart size, heart rate, or owner-perceived quality of life.[53] It is possible that a greater effect might be observed if the medication was given over a longer period of time or at a higher dose. Overall, the use of beta-blockers for the canine patient with DCM has not yet been well studied and a consensus opinion on use of these drugs for the canine patient 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 if there is evidence of heart failure until it is very well stabilized. It cannot be overemphasized that the addition of beta-blockers in canine DCM patients should be done very cautiously with gradual increases in dosing after a 2-week period and careful monitoring of heart rate, blood pressure, and symptoms.

Answer 30

Administration of beta-blockers to the dog in the occult stage of DCM for a cardioprotective effect is still being evaluated. The addition of low-dose beta-blockers to the treatment of human patients with DCM and stable heart failure has demonstrated a reduction in both mortality and morbidity.[52] However, many human patients with DCM cannot tolerate even very low doses of beta-blockers and demonstrate rapid cardiac decompensation. One prospective, placebo-controlled canine study that looked at the effect of 3 months of the beta-blocker carvedilol at a gradually increasing dose did not identify any differences between the beta-blocker and placebo effect in echocardiographic indices of left ventricular size or function, neurohormonal activation, radiographic heart size, heart rate, or owner-perceived quality of life.[53] It is possible that a greater effect might be observed if the medication was given over a longer period of time or at a higher dose. Overall, the use of beta-blockers for the canine patient with DCM has not yet been well studied and a consensus opinion on use of these drugs for the canine patient 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 if there is evidence of heart failure until it is very well stabilized. It cannot be overemphasized that the addition of beta-blockers in canine DCM patients should be done very cautiously with gradual increases in dosing after a 2-week period and careful monitoring of heart rate, blood pressure, and symptoms.

Question 31

Treatment of the Dog with Dilated Cardiomyopathy and Congestive Heart Failure Dogs with DCM and heart failure will benefit from inotropic support. Ideally, this would be with pimobendan, a phosphodiesterase III and V inhibitor with calcium-sensitizing properties that acts as a positive inotrope, as well as vasodilator (inodilator).[54] Pimobendan has balanced vasodilatation and positive inotropic effects and has been shown to increase survival (median of 130 days versus a median of 14 days for the placebo in one study) in Doberman Pinschers with DCM when given at a dose of approximately 0.25 mg/kg orally q 12 hours.[54],[55] Additional medications for heart failure such as ACE inhibitors and diuretics should be started as needed. Nonspecific treatments including nutritional supplementation such as taurine should be considered in dogs that may be suspected as having low levels until proven otherwise.[56] Supplementation with fatty acids may be considered for patients with cachexia.

Answer 31

Treatment of the Dog with Dilated Cardiomyopathy and Congestive Heart Failure Dogs with DCM and heart failure will benefit from inotropic support. Ideally, this would be with pimobendan, a phosphodiesterase III and V inhibitor with calcium-sensitizing properties that acts as a positive inotrope, as well as vasodilator (inodilator).[54] Pimobendan has balanced vasodilatation and positive inotropic effects and has been shown to increase survival (median of 130 days versus a median of 14 days for the placebo in one study) in Doberman Pinschers with DCM when given at a dose of approximately 0.25 mg/kg orally q 12 hours.[54],[55] Additional medications for heart failure such as ACE inhibitors and diuretics should be started as needed. Nonspecific treatments including nutritional supplementation such as taurine should be considered in dogs that may be suspected as having low levels until proven otherwise.[56] Supplementation with fatty acids may be considered for patients with cachexia.

Question 32

Treatment of the Dog with Ventricular Arrhythmias There is little consensus for the decision of when and how to treat ventricular arrhythmias in the dog with DCM. Rapid ventricular tachycardia, complex ventricular arrhythmias, or the combination of ventricular arrhythmias, ventricular dilation, and systolic dysfunction are thought to be associated with a higher risk of sudden cardiac death and to be indications for treatment, but this has not been well studied. 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 antiarrhythmics. Sotalol, a combination beta-blocker and potassium channel blocker, may be beneficial in some cases but should be used a bit more cautiously (low dose) if systolic dysfunction is present. Mexiletine at a dose of 5 to 6 mg/kg, q 8 hours, orally can be very effective at decreasing the arrhythmia. In a small number of cases it can cause nausea but this can be significantly reduced if it is given with at least a small meal, so it should never be given on an empty stomach. Amiodarone has been studied in the affected Doberman Pinscher at a dose of 10.0 mg/kg orally q 12 hours for 5 days and then 5.0 mg/kg q 24 hours. Careful evaluation of serum concentrations, complete blood counts (neutropenia has been reported), and liver enzymes on a monthly basis is suggested.[42] 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 has not been well studied.

Answer 32

Treatment of the Dog with Ventricular Arrhythmias There is little consensus for the decision of when and how to treat ventricular arrhythmias in the dog with DCM. Rapid ventricular tachycardia, complex ventricular arrhythmias, or the combination of ventricular arrhythmias, ventricular dilation, and systolic dysfunction are thought to be associated with a higher risk of sudden cardiac death and to be indications for treatment, but this has not been well studied. 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 antiarrhythmics. Sotalol, a combination beta-blocker and potassium channel blocker, may be beneficial in some cases but should be used a bit more cautiously (low dose) if systolic dysfunction is present. Mexiletine at a dose of 5 to 6 mg/kg, q 8 hours, orally can be very effective at decreasing the arrhythmia. In a small number of cases it can cause nausea but this can be significantly reduced if it is given with at least a small meal, so it should never be given on an empty stomach. Amiodarone has been studied in the affected Doberman Pinscher at a dose of 10.0 mg/kg orally q 12 hours for 5 days and then 5.0 mg/kg q 24 hours. Careful evaluation of serum concentrations, complete blood counts (neutropenia has been reported), and liver enzymes on a monthly basis is suggested.[42] 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 has not been well studied.

Question 33

Prognosis for the Dog with Dilated Cardiomyopathy Prognosis is likely to be dependent on the underlying cause, which is generally not known. However, for the canine population with DCM, certain negative predictors of survival have been identified including age of onset of clinical signs, pleural effusion, pulmonary edema, ascites, atrial fibrillation, end-systolic volume index, ejection fraction, and a restrictive pattern of transmitral flow.[57],[58]

Answer 33

Prognosis for the Dog with Dilated Cardiomyopathy Prognosis is likely to be dependent on the underlying cause, which is generally not known. However, for the canine population with DCM, certain negative predictors of survival have been identified including age of onset of clinical signs, pleural effusion, pulmonary edema, ascites, atrial fibrillation, end-systolic volume index, ejection fraction, and a restrictive pattern of transmitral flow.[57],[58]

Question 34

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY IN THE BOXER Since the early 1980s, the term Boxer cardiomyopathy has been used to describe adult Boxer dogs that present with ventricular arrhythmias and, sometimes, syncope.[59] Recent studies have demonstrated that the disease has many similarities to a human disease called arrhythmogenic right ventricular cardiomyopathy (ARVC). The similarities between the diseases include clinical presentation, etiology, and a fairly unique histopathology that includes a fibrous fatty infiltrate of the right ventricular free wall[60] (Figure 251-5). The disease is most commonly character.....................,...................,and..............However, ............... dysfunction and ventricular ................ are seen in a small percentage of cases.

Answer 34

Since the early 1980s, the term Boxer cardiomyopathy has been used to describe adult Boxer dogs that present with ventricular arrhythmias and, sometimes, syncope.[59] Recent studies have demonstrated that the disease has many similarities to a human disease called arrhythmogenic right ventricular cardiomyopathy (ARVC). The similarities between the diseases include clinical presentation, etiology, and a fairly unique histopathology that includes a fibrous fatty infiltrate of the right ventricular free wall[60] (Figure 251-5). The disease is most commonly characterized by ventricular arrhythmias, syncope, and sudden death. However, systolic dysfunction and ventricular dilation are seen in a small percentage of cases.

Question 35

Figure 251-5 Histopathologic sample of the right ventricular wall from a Boxer dog with arrhythmogenic right ventricular cardiomyopathy demonstrates multifocal myocyte vacuolization, myocyte loss, and significant fatty infiltration. 20× magnification, hematoxylin and eosin stain.

Answer 35

Figure 251-5 Histopathologic sample of the right ventricular wall from a Boxer dog with arrhythmogenic right ventricular cardiomyopathy demonstrates multifocal myocyte vacuolization, myocyte loss, and significant fatty infiltration. 20× magnification, hematoxylin and eosin stain.

Question 36

ARVC is a familial disease in the Boxer and appears to be inherited as an autosomal dominant trait. Unfortunately, the disease also appears to be a disease of variable genetic penetrance and affected dogs can have many different presentations including asymptomatic, syncope, sudden death, and ............. dysfunction with CHF.

Answer 36

ARVC is a familial disease in the Boxer and appears to be inherited as an autosomal dominant trait. Unfortunately, the disease also appears to be a disease of variable genetic penetrance and affected dogs can have many different presentations including asymptomatic, syncope, sudden death, and systolic dysfunction with CHF.

Question 37

DIAGNOSIS The most common presenting complaint is one of syncope. Episodes of syncope may be associated with a period of exercise or excitement, but are not always. Some dogs present for exercise intolerance or lethargy and others die suddenly without ever developing symptoms. Infrequently (approximately 10% of affected dogs), a dog may present with signs of left or biventricular heart failure.

Answer 37

The most common presenting complaint is one of syncope. Episodes of syncope may be associated with a period of exercise or excitement, but are not always. Some dogs present for exercise intolerance or lethargy and others die suddenly without ever developing symptoms. Infrequently (approximately 10% of affected dogs), a dog may present with signs of left or biventricular heart failure.

Question 38

Most affected Boxers have a completely normal physical examination. However, a tachyarrhythmia may be auscultated. In the small percentage of cases with ventricular dilation and systolic dysfunction, a systolic murmur and/or gallop (S3) may be auscultated at the left apex. Infrequently, signs of right heart failure (ascites and jugular venous distension) may be observed. The Boxer breed also has a very high incidence of left basilar systolic murmurs. These murmurs may be associated with aortic stenosis, or potentially may be physiologic. Many Boxers with ARVC have these murmurs in addition to their arrhythmic disease, but left basilar systolic heart murmurs are not an indication of Boxer ARVC.

Answer 38

Most affected Boxers have a completely normal physical examination. However, a tachyarrhythmia may be auscultated. In the small percentage of cases with ventricular dilation and systolic dysfunction, a systolic murmur and/or gallop (S3) may be auscultated at the left apex. Infrequently, signs of right heart failure (ascites and jugular venous distension) may be observed. The Boxer breed also has a very high incidence of left basilar systolic murmurs. These murmurs may be associated with aortic stenosis, or potentially may be physiologic. Many Boxers with ARVC have these murmurs in addition to their arrhythmic disease, but left basilar systolic heart murmurs are not an indication of Boxer ARVC.

Question 39

Biomarkers appear to be of variable value in the diagnosis of Boxer ARVC. Cardiac troponin I has been shown to be significantly elevated in Boxers with ARVC and correlated with both VPC number and grade, or complexity of the arrhythmia[62] (Figure 251-6). However, some affected dogs had lower levels of cTnI that overlapped with normal Boxers. Therefore, although measurement of cTnI may provide supportive information in a dog in which a diagnosis of ARVC is suspected, further study is necessary before it can be utilized as an independent screening test. Brain natriuretic peptide measurement in similar groups of Boxers did not identify a difference in affected dogs in comparison with normal Boxers and normal unaffected Boxers; therefore BNP does not appear to be a useful indicator of disease.[63]

Answer 39

Biomarkers appear to be of variable value in the diagnosis of Boxer ARVC. Cardiac troponin I has been shown to be significantly elevated in Boxers with ARVC and correlated with both VPC number and grade, or complexity of the arrhythmia[62] (Figure 251-6). However, some affected dogs had lower levels of cTnI that overlapped with normal Boxers. Therefore, although measurement of cTnI may provide supportive information in a dog in which a diagnosis of ARVC is suspected, further study is necessary before it can be utilized as an independent screening test. Brain natriuretic peptide measurement in similar groups of Boxers did not identify a difference in affected dogs in comparison with normal Boxers and normal unaffected Boxers; therefore BNP does not appear to be a useful indicator of disease.[63]

Question 40

A 2- to 5-minute electrocardiogram is frequently normal in the affected Boxer; however, VPCs may be present singly, in pairs, and in runs of paroxysmal ventricular tachycardia (Figure 251-7). The VPCs typically have a ..........bundle branch block morphology in leads I, II, III, and AVF, consistent with the right ventricular origin of this arrhythmia.[64] In some cases, the ventricular arrhythmias that cause syncope may not be observed on the electrocardiogram and a 24-hour Holter monitor should be performed to evaluate for arrhythmias.

Answer 40

A 2- to 5-minute electrocardiogram is frequently normal in the affected Boxer; however, VPCs may be present singly, in pairs, and in runs of paroxysmal ventricular tachycardia (Figure 251-7). The VPCs typically have a left bundle branch block morphology in leads I, II, III, and AVF, consistent with the right ventricular origin of this arrhythmia.[64] In some cases, the ventricular arrhythmias that cause syncope may not be observed on the electrocardiogram and a 24-hour Holter monitor should be performed to evaluate for arrhythmias.

Question 41

Interpretation of the Holter results can sometimes be challenging because strict criteria for this diagnosis do not exist. However, because it is unusual for a normal dog to have any VPCs in a 24-hour period, the observation of >100 VPCs, or periods of couplets, triplets, or runs of ventricular tachycardia are abnormal and may be diagnostic in a dog with clinical signs.[65] Supraventricular premature complexes may also be observed, particularly in Boxers with ventricular dilation and systolic dysfunction.

Answer 41

Interpretation of the Holter results can sometimes be challenging because strict criteria for this diagnosis do not exist. However, because it is unusual for a normal dog to have any VPCs in a 24-hour period, the observation of >100 VPCs, or periods of couplets, triplets, or runs of ventricular tachycardia are abnormal and may be diagnostic in a dog with clinical signs.[65] Supraventricular premature complexes may also be observed, particularly in Boxers with ventricular dilation and systolic dysfunction.

Question 42

Thoracic radiographs are usually within normal limits. However, in the small number of cases with left ventricular dilation and systolic dysfunction, generalized cardiomegaly with pulmonary edema and/or pleural effusion may be noted.

Answer 42

Thoracic radiographs are usually within normal limits. However, in the small number of cases with left ventricular dilation and systolic dysfunction, generalized cardiomegaly with pulmonary edema and/or pleural effusion may be noted.

Question 43

Echocardiography is an important part of the evaluation because ventricular dilation and systolic dysfunction may occur, but in most cases affected dogs have normal chamber sizes and systolic function. In some cases, careful evaluation will allow the identification of right ventricular enlargement

Answer 43

Echocardiography is an important part of the evaluation because ventricular dilation and systolic dysfunction may occur, but in most cases affected dogs have normal chamber sizes and systolic function. In some cases, careful evaluation will allow the identification of right ventricular enlargement

Question 44

The familial etiology of ARVC has led to a widespread interest in screening dogs before selecting them as breeding animals. Because ARVC presents as an electrical abnormality more often than one of myocardial dysfunction, screening efforts should be based on annual Holter monitoring and annual echocardiography. Unfortunately, clear criteria for the diagnosis of occult ARVC do not exist. However, dogs that are symptomatic (syncope, heart failure) or have evidence of ventricular tachycardia on a Holter should not be used for breeding. Additionally, dogs that have over 100 left bundle branch block morphology VPCs/24 hours are probably highly suspicious of being affected. However, not all affected dogs will ever develop clinical signs and many may live a normal lifespan. It is likely that there are multiple factors that may influence which dogs become symptomatic for the disease. To help decrease the risk of making an error when adding or removing a dog from a breeding program, owners should be encouraged to screen annually rather than putting significant emphasis on a single Holter monitor reading. Because the disease is adult onset and an increase in VPCs has been observed with age in affected animals, an animal that is clear at the age of 2 is not guaranteed to stay clear. Additionally, an animal with a few hundred VPCs at the age of 2 years may have more, less, or the same number the next year. Until a greater understanding of disease inheritance and disease progression exists, caution should be used when advising breeders to remove dogs from breeding programs. Overzealous removal of animals based on the results of a single Holter monitor may have a significant negative impact on the breed.

Answer 44

The familial etiology of ARVC has led to a widespread interest in screening dogs before selecting them as breeding animals. Because ARVC presents as an electrical abnormality more often than one of myocardial dysfunction, screening efforts should be based on annual Holter monitoring and annual echocardiography. Unfortunately, clear criteria for the diagnosis of occult ARVC do not exist. However, dogs that are symptomatic (syncope, heart failure) or have evidence of ventricular tachycardia on a Holter should not be used for breeding. Additionally, dogs that have over 100 left bundle branch block morphology VPCs/24 hours are probably highly suspicious of being affected. However, not all affected dogs will ever develop clinical signs and many may live a normal lifespan. It is likely that there are multiple factors that may influence which dogs become symptomatic for the disease. To help decrease the risk of making an error when adding or removing a dog from a breeding program, owners should be encouraged to screen annually rather than putting significant emphasis on a single Holter monitor reading. Because the disease is adult onset and an increase in VPCs has been observed with age in affected animals, an animal that is clear at the age of 2 is not guaranteed to stay clear. Additionally, an animal with a few hundred VPCs at the age of 2 years may have more, less, or the same number the next year. Until a greater understanding of disease inheritance and disease progression exists, caution should be used when advising breeders to remove dogs from breeding programs. Overzealous removal of animals based on the results of a single Holter monitor may have a significant negative impact on the breed.

Question 45

TREATMENT If an arrhythmia is detected on routine examination in an asymptomatic dog a Holter monitor should be performed to evaluate for the frequency and complexity of the arrhythmia. Although a strict relationship between the development of symptoms and the number of VPCs does not exist, treatment is generally started if >1000 VPCs/24 hours, runs of ventricular tachycardia, or evidence of the R on T phenomenon exist. Owners should be advised that ventricular antiarrhythmics have the potential for proarrhythmic effects and that treatment is not known to decrease risk of sudden death. At this time, there is no evidence that treatment will significantly alter the outcome for affected dogs. However, treatment has been shown to decrease the number of VPCs and syncopal episodes.[66] Dogs with syncope and ventricular arrhythmias are generally started on treatment. There are two choices for treatment that are well tolerated and have been shown to decrease VPC number and complexity, sotalol at a dose of 1.5 to 2.5 mg/kg, q 12 hours or mexiletine at a dose of 5 to 6 mg/kg, q 8 hours, orally.[66] In some cases the combination of sotalol and mexiletine at these doses is indicated for optimal control of the arrhythmia. It is likely that there is individual variation for drug response and if a poor response is observed with one drug, a different one or the combination of the two may prove to be more effective. Ideally, a Holter monitor would be placed before starting therapy and repeated 2 to 3 weeks after starting therapy to monitor the effect of the medication. Significant day-to-day variation in VPC number exists, but a therapeutic effect is likely to exist if at least an 85% reduction in VPC number is observed on medication.[67]

Answer 45

TREATMENT If an arrhythmia is detected on routine examination in an asymptomatic dog a Holter monitor should be performed to evaluate for the frequency and complexity of the arrhythmia. Although a strict relationship between the development of symptoms and the number of VPCs does not exist, treatment is generally started if >1000 VPCs/24 hours, runs of ventricular tachycardia, or evidence of the R on T phenomenon exist. Owners should be advised that ventricular antiarrhythmics have the potential for proarrhythmic effects and that treatment is not known to decrease risk of sudden death. At this time, there is no evidence that treatment will significantly alter the outcome for affected dogs. However, treatment has been shown to decrease the number of VPCs and syncopal episodes.[66] Dogs with syncope and ventricular arrhythmias are generally started on treatment. There are two choices for treatment that are well tolerated and have been shown to decrease VPC number and complexity, sotalol at a dose of 1.5 to 2.5 mg/kg, q 12 hours or mexiletine at a dose of 5 to 6 mg/kg, q 8 hours, orally.[66] In some cases the combination of sotalol and mexiletine at these doses is indicated for optimal control of the arrhythmia. It is likely that there is individual variation for drug response and if a poor response is observed with one drug, a different one or the combination of the two may prove to be more effective. Ideally, a Holter monitor would be placed before starting therapy and repeated 2 to 3 weeks after starting therapy to monitor the effect of the medication. Significant day-to-day variation in VPC number exists, but a therapeutic effect is likely to exist if at least an 85% reduction in VPC number is observed on medication.[67]

Question 46

In one study, fish oils (78 mg EPA and 497 mg DHA per day) given for 6 weeks were shown to decrease the number of VPCs but not to a degree that was beyond what might be due to day-to-day variation. Thus antiarrhythmics are likely still indicated for management.[68]

Answer 46

In one study, fish oils (78 mg EPA and 497 mg DHA per day) given for 6 weeks were shown to decrease the number of VPCs but not to a degree that was beyond what might be due to day-to-day variation. Thus antiarrhythmics are likely still indicated for management.[68]

Question 47

If echocardiography demonstrates systolic dysfunction and ventricular dilation, treatment for DCM (pimobendan, ACE inhibitors, diuretics) may be warranted. Additionally, supplementation with L-carnitine might be considered at a dose of 50 mg/kg, q 8 to 12 hours, orally, because a small number of affected Boxers have demonstrated improvement in systolic function and prognosis after supplementation.[33] Dogs with ARVC are always at risk of dying of sudden cardiac death. Many dogs may live for years on antiarrhythmics without symptoms, but some of these may eventually develop ventricular dilation and systolic dysfunction.

Answer 47

If echocardiography demonstrates systolic dysfunction and ventricular dilation, treatment for DCM (pimobendan, ACE inhibitors, diuretics) may be warranted. Additionally, supplementation with L-carnitine might be considered at a dose of 50 mg/kg, q 8 to 12 hours, orally, because a small number of affected Boxers have demonstrated improvement in systolic function and prognosis after supplementation.[33] Dogs with ARVC are always at risk of dying of sudden cardiac death. Many dogs may live for years on antiarrhythmics without symptoms, but some of these may eventually develop ventricular dilation and systolic dysfunction.

Question 48

MYOCARDITIS Myocarditis is a form of myocardial disease characterized by the presence of myocardial necrosis or degeneration and inflammation. A variety of physical, chemical, and infectious agents can damage the myocardial tissue and evoke an inflammatory response that may result in chamber enlargement, myocardial dysfunction similar to that observed in DCM, and a variety of tachyarrhythmias and bradyarrhhthmias. Plasma troponin I (cTnI) levels are often elevated, suggesting myocardial injury. In the dog, protozoal and viral organisms are reported most commonly.

Answer 48

Myocarditis is a form of myocardial disease characterized by the presence of myocardial necrosis or degeneration and inflammation. A variety of physical, chemical, and infectious agents can damage the myocardial tissue and evoke an inflammatory response that may result in chamber enlargement, myocardial dysfunction similar to that observed in DCM, and a variety of tachyarrhythmias and bradyarrhhthmias. Plasma troponin I (cTnI) levels are often elevated, suggesting myocardial injury. In the dog, protozoal and viral organisms are reported most commonly.

Question 49

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is common in the dog, particularly in the southern part of North America. Three stages of infection have been described: acute, latent, and chronic. The acute stage is characterized by lethargy, generalized lymphadenopathy, pale mucous membranes, increased capillary refill time, and hepato-splenomegaly.[71] This stage is associated with a variety of electrocardiographic abnormalities including sinus tachycardia, prolonged PR interval, decreased R wave amplitude, axis shifts, and conduction disturbances.[72] Sudden death may be observed. Dogs that survive the acute stage may enter a prolonged latent period during which the clinical signs appear to regress.[72] The chronic stage of Chagas disease is associated with signs of progressive right-sided cardiac dysfunction, ascites, pleural effusion, hepatomegaly, and jugular venous distention. Occasional ventricular tachycardias have been reported.[72] In one study, almost half of the dogs diagnosed histopathologically with Chagas myocarditis at necropsy were dogs that died suddenly and 50% of those dogs were younger than 1 year of age.[70] The diagnosis of Chagas disease is most commonly performed by serology, and the acute form can sometimes be diagnosed by the presence of circulating trypomastigotes on thick blood smears. In general, treatment of Chagas disease is directed at palliation of clinical signs because destruction of the intracellular form of the parasite may result in severe exacerbation of the host inflammatory response. However, preliminary work in dogs suggests that a cysteine protease inhibitor may be very effective for reducing the severity of the cardiac aspects of the disease.[73]

Answer 49

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is common in the dog, particularly in the southern part of North America. Three stages of infection have been described: acute, latent, and chronic. The acute stage is characterized by lethargy, generalized lymphadenopathy, pale mucous membranes, increased capillary refill time, and hepato-splenomegaly.[71] This stage is associated with a variety of electrocardiographic abnormalities including sinus tachycardia, prolonged PR interval, decreased R wave amplitude, axis shifts, and conduction disturbances.[72] Sudden death may be observed. Dogs that survive the acute stage may enter a prolonged latent period during which the clinical signs appear to regress.[72] The chronic stage of Chagas disease is associated with signs of progressive right-sided cardiac dysfunction, ascites, pleural effusion, hepatomegaly, and jugular venous distention. Occasional ventricular tachycardias have been reported.[72] In one study, almost half of the dogs diagnosed histopathologically with Chagas myocarditis at necropsy were dogs that died suddenly and 50% of those dogs were younger than 1 year of age.[70] The diagnosis of Chagas disease is most commonly performed by serology, and the acute form can sometimes be diagnosed by the presence of circulating trypomastigotes on thick blood smears. In general, treatment of Chagas disease is directed at palliation of clinical signs because destruction of the intracellular form of the parasite may result in severe exacerbation of the host inflammatory response. However, preliminary work in dogs suggests that a cysteine protease inhibitor may be very effective for reducing the severity of the cardiac aspects of the disease.[73]

Question 50

Leishmania are protozoal organisms that are endemic in certain geographic regions including the Mediterranean basin.[74] Clinical signs of the myocarditis associated with Leishmania are thought to be a result of direct action of the parasite within the myocardium and intense inflammation in response to the parasite. Cardiac arrhythmias including first-degree AV block have been observed and both epicarditis and myocarditis have been identified at necropsy. Additional protozoan parasites that have been associated with the development of myocarditis include Neospora caninum and Toxoplasmosis gondii.[75-77]

Answer 50

Leishmania are protozoal organisms that are endemic in certain geographic regions including the Mediterranean basin.[74] Clinical signs of the myocarditis associated with Leishmania are thought to be a result of direct action of the parasite within the myocardium and intense inflammation in response to the parasite. Cardiac arrhythmias including first-degree AV block have been observed and both epicarditis and myocarditis have been identified at necropsy. Additional protozoan parasites that have been associated with the development of myocarditis include Neospora caninum and Toxoplasmosis gondii.[75-77]

Question 51

Parvovirus myocarditis is an uncommon form of myocardial disease. It may present with a per-acute form that affects puppies between 3 and 8 weeks of age. Puppies present with acute dyspnea consistent with severe left heart failure and die within hours. At necropsy, the hearts are found to be dilated with multifocal myofiber necrosis, mononuclear cell infiltrate, and intranuclear inclusion bodies in the myocardial nuclei. A second form of the disease affects juvenile dogs (generally younger than 1 year of age) and has a clinical presentation similar to that of DCM.

Answer 51

Parvovirus myocarditis is an uncommon form of myocardial disease. It may present with a per-acute form that affects puppies between 3 and 8 weeks of age. Puppies present with acute dyspnea consistent with severe left heart failure and die within hours.[31] At necropsy, the hearts are found to be dilated with multifocal myofiber necrosis, mononuclear cell infiltrate, and intranuclear inclusion bodies in the myocardial nuclei.[31],[78] A second form of the disease affects juvenile dogs (generally younger than 1 year of age) and has a clinical presentation similar to that of DCM.

Question 52

West Nile virus has been observed uncommonly in the dog, and clinical signs are often vague including lethargy, inappetence, neurologic signs, arrhythmias, and a fever.[79],[80] Severe lymphocytic, neutrophilic myocarditis and vasculitis have been observed with focally extensive hemorrhage and myonecrosis. The diagnosis can be confirmed in a variety of ways including immunohistochemistry, RT-PCR, virus isolation, and serology.[79]

Answer 52

West Nile virus has been observed uncommonly in the dog, and clinical signs are often vague including lethargy, inappetence, neurologic signs, arrhythmias, and a fever.[79],[80] Severe lymphocytic, neutrophilic myocarditis and vasculitis have been observed with focally extensive hemorrhage and myonecrosis. The diagnosis can be confirmed in a variety of ways including immunohistochemistry, RT-PCR, virus isolation, and serology.[79]

Question 53

Fungal myocarditis due to Blastomycosis has been reported, although this does not appear to be a common form of the fungal infection.[81] Three dogs presented for syncope, one for sudden death and three had newly diagnosed heart murmurs. Cardiac findings included sinus tachycardia, as well as one dog with ST segment elevation and one dog with third-degree AV block. Two dogs had cardiac compression due to an extracardiac granuloma, whereas others had either myocardial, epicardial, pericardial, or valvular involvement. Although only a small number of cases have been reported, generally the dogs with cardiac involvement of Blastomycosis had a poor prognosis.

Answer 53

Fungal myocarditis due to Blastomycosis has been reported, although this does not appear to be a common form of the fungal infection.[81] Three dogs presented for syncope, one for sudden death and three had newly diagnosed heart murmurs. Cardiac findings included sinus tachycardia, as well as one dog with ST segment elevation and one dog with third-degree AV block. Two dogs had cardiac compression due to an extracardiac granuloma, whereas others had either myocardial, epicardial, pericardial, or valvular involvement. Although only a small number of cases have been reported, generally the dogs with cardiac involvement of Blastomycosis had a poor prognosis.

Question 54

Infrequently, infectious organisms including bacteria, Bacillus piliformis, Citrobacter koseri, and the spirochete Borrelia burgdorferi have been associated with the development of myocarditis.[82],[83]

Answer 54

Infrequently, infectious organisms including bacteria, Bacillus piliformis, Citrobacter koseri, and the spirochete Borrelia burgdorferi have been associated with the development of myocarditis.[82],[83]

Question 55

Atrial Myocarditis A form of myocarditis limited to the atria has been reported.[84-86] Unexplained atrial arrhythmias including atrial fibrillation have been associated with inflammation or infectious organisms in the atria. Multifocal myocarditis of both atria was observed at necropsy in a case with atrial fibrillation.[84] Intermittent asystole with syncope was observed in a dog with lymphocytes, macrophages, and neutrophils throughout the right and, to a lesser extent, left atrium.[85] One case of atrial myocarditis was associated with a concurrent diagnosis of polymyositis.[86] The dog had significant right atrial dilation, atrial premature complexes, and increased troponin levels. Histopathologic analysis identified right atrial lymphocytic infiltration.

Answer 55

Atrial Myocarditis A form of myocarditis limited to the atria has been reported.[84-86] Unexplained atrial arrhythmias including atrial fibrillation have been associated with inflammation or infectious organisms in the atria. Multifocal myocarditis of both atria was observed at necropsy in a case with atrial fibrillation.[84] Intermittent asystole with syncope was observed in a dog with lymphocytes, macrophages, and neutrophils throughout the right and, to a lesser extent, left atrium.[85] One case of atrial myocarditis was associated with a concurrent diagnosis of polymyositis.[86] The dog had significant right atrial dilation, atrial premature complexes, and increased troponin levels. Histopathologic analysis identified right atrial lymphocytic infiltration.

Question 56

HYPERTROPHIC CARDIOMYOPATHY Hypertrophic cardiomyopathy is a primary myocardial disease characterized by concentric hypertrophy of the interventricular septum and left ventricular free wall. Hypertrophic cardiomyopathy and the variant hypertrophic obstructive cardiomyopathy are infrequent forms of canine myocardial disease. There appear to be significant differences between the canine disease and the disease more commonly observed in cats and human beings with regard to etiology and pathologic findings.[87],[88] An inheritable form of hypertrophic obstructive cardiomyopathy has been observed in the Pointer dog, but most canine cases appear to be sporadic.[87-90] Because of the relative infrequency that hypertrophic and hypertrophic obstructive cardiomyopathy is observed in the dog, suspect patients should be carefully evaluated for other causes of concentric hypertrophy of the left ventricle including the much more common left ventricular outflow tract obstruction observed with subvalvular and valvular aortic stenosis

Answer 56

HYPERTROPHIC CARDIOMYOPATHY Hypertrophic cardiomyopathy is a primary myocardial disease characterized by concentric hypertrophy of the interventricular septum and left ventricular free wall. Hypertrophic cardiomyopathy and the variant hypertrophic obstructive cardiomyopathy are infrequent forms of canine myocardial disease. There appear to be significant differences between the canine disease and the disease more commonly observed in cats and human beings with regard to etiology and pathologic findings.[87],[88] An inheritable form of hypertrophic obstructive cardiomyopathy has been observed in the Pointer dog, but most canine cases appear to be sporadic.[87-90] Because of the relative infrequency that hypertrophic and hypertrophic obstructive cardiomyopathy is observed in the dog, suspect patients should be carefully evaluated for other causes of concentric hypertrophy of the left ventricle including the much more common left ventricular outflow tract obstruction observed with subvalvular and valvular aortic stenosis

Question 57

HYPOTHYROIDISM Some dogs with hypothyroidism have been observed to have a reduction in fractional shortening percentage and an increase in left ventricular dimensions; however, the values had significant overlap with normal dogs.[91] Thus, although evaluation of thyroid levels might be considered in dogs that have minor echocardiographic changes in addition to other signs of hypothyroidism, it should not be considered a common cause of myocardial dysfunction or ventricular dilation.[92]

Answer 57

HYPOTHYROIDISM Some dogs with hypothyroidism have been observed to have a reduction in fractional shortening percentage and an increase in left ventricular dimensions; however, the values had significant overlap with normal dogs.[91] Thus, although evaluation of thyroid levels might be considered in dogs that have minor echocardiographic changes in addition to other signs of hypothyroidism, it should not be considered a common cause of myocardial dysfunction or ventricular dilation.[92]

Question 58

MYOCARDIAL INFARCTION Acute myocardial infarctions are an uncommon form of myocardial disease and appear to be most commonly associated with concurrent systemic or cardiac disease that has led to a thromboembolic state. These conditions might include endocarditis, neoplasia, renal disease, immune-mediated hemolytic anemia, and pancreatic disease. Dogs with infarcts were very rarely diagnosed with atherosclerosis as opposed to human beings who have a high incidence of infarcts associated with atherosclerosis

Answer 58

MYOCARDIAL INFARCTION Acute myocardial infarctions are an uncommon form of myocardial disease and appear to be most commonly associated with concurrent systemic or cardiac disease that has led to a thromboembolic state. These conditions might include endocarditis, neoplasia, renal disease, immune-mediated hemolytic anemia, and pancreatic disease. Dogs with infarcts were very rarely diagnosed with atherosclerosis as opposed to human beings who have a high incidence of infarcts associated with atherosclerosis