Myocardial Disease : Feline- Ettinger

Question 1

Cardiomyopathy is defined as primary heart muscle disease associated with cardiac dysfunction. The World Health Organization (WHO) task force has classified cardiomyopathies in human medicine into the following categories: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and unclassified cardiomyopathy (UCM) (for any cardiomyopathy not fitting within the previous categories).[1]

Answer 1

Cardiomyopathy is defined as primary heart muscle disease associated with cardiac dysfunction. The World Health Organization (WHO) task force has classified cardiomyopathies in human medicine into the following categories: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and unclassified cardiomyopathy (UCM) (for any cardiomyopathy not fitting within the previous categories).[1]

Question 2

The WHO also includes a category of “specific” cardiomyopathies to describe systemic disorders that lead to heart muscle disease, but the term has recently been proposed to be changed to “secondary” cardiomyopathies by a consensus panel within the American Heart Association. Causes of secondary cardiomyopathy in cats include?

Answer 2

Thyrotoxicosis, systemic hypertension, and acromegaly, which lead to concentric left ventricular (LV) hypertrophy.

Toxic myocardial reactions such as anthracycline-induced myocardial failure lead to secondary cardiomyopathy and myocardial failure.

Nutritional disorders in veterinary medicine that lead to a secondary cardiomyopathy include taurine deficiency, carnitine deficiency, and selenium deficiency.

Question 3

Feline cardiomyopathies are the most common cause of heart disease in cats. Of 408 cats presenting for cardiology workup, 62% were diagnosed with a primary cardiomyopathy.[1] The most common feline cardiomyopathy is HCM, which accounts for approximately 58% to 68% of feline cardiomyopathy cases.[1],[2] RCM and UCM are the next most common categories (21% and 10%, respectively), followed by DCM (10%).[2] ARVC is very rare and accounted for less than 1% of feline cardiomyopathy cases.[1]

Answer 3

Feline cardiomyopathies are the most common cause of heart disease in cats. Of 408 cats presenting for cardiology workup, 62% were diagnosed with a primary cardiomyopathy.[1] The most common feline cardiomyopathy is HCM, which accounts for approximately 58% to 68% of feline cardiomyopathy cases.[1],[2] RCM and UCM are the next most common categories (21% and 10%, respectively), followed by DCM (10%).[2] ARVC is very rare and accounted for less than 1% of feline cardiomyopathy cases.[1]

Question 4

Echocardiography is required for the diagnosis of the specific cardiomyopathy (Table 252-1). Thoracic radiographs may show cardiomegaly and possibly heart failure in cats with significant cardiac disease, but changes are not diagnostic for a specific cardiomyopathy. Pulmonary edema occurs once the LV diastolic filling pressure and left atrial pressure exceed 20 to 25 mm Hg. Pleural effusion occurs secondary to severe left or right heart disease, or a combination of both. Pulmonary venous distension is often seen in cats with left heart failure. Dilation of the caudal vena cava and ascites is seen with right heart failure.

Answer 4

Echocardiography is required for the diagnosis of the specific cardiomyopathy (Table 252-1). Thoracic radiographs may show cardiomegaly and possibly heart failure in cats with significant cardiac disease, but changes are not diagnostic for a specific cardiomyopathy. Pulmonary edema occurs once the LV diastolic filling pressure and left atrial pressure exceed 20 to 25 mm Hg. Pleural effusion occurs secondary to severe left or right heart disease, or a combination of both. Pulmonary venous distension is often seen in cats with left heart failure. Dilation of the caudal vena cava and ascites is seen with right heart failure.

Question 5

HYPERTROPHIC CARDIOMYOPATHY

HCM is the most common heart disease of cats and also the most common feline cardiomyopathy, comprising approximately 58% to 68% of cardiomyopathy cases.[1],[2] It is defined as LV concentric hypertrophy in the absence of other causes of concentric hypertrophy such as aortic stenosis, systemic hypertension, hyperthyroidism, or acromegaly. HCM is a primary myocardial disease, caused by a sarcomeric defect within the cardiomyocytes.

Answer 5

HYPERTROPHIC CARDIOMYOPATHY

HCM is the most common heart disease of cats and also the most common feline cardiomyopathy, comprising approximately 58% to 68% of cardiomyopathy cases.[1],[2] It is defined as LV concentric hypertrophy in the absence of other causes of concentric hypertrophy such as aortic stenosis, systemic hypertension, hyperthyroidism, or acromegaly. HCM is a primary myocardial disease, caused by a sarcomeric defect within the cardiomyocytes.

Question 6

Genetics of Hypertrophic Cardiomyopathy

In people, 66% of HCM cases are due to a familial heritable ………………. defect, and the remaining cases are ………………. ………………….. There is a familial heritability in some purebred cats including an ………… ……………. ……….. in the Ragdoll cat, Maine Coon cat, and American Shorthair cat. Maine Coon cats have an …………… ……………. pattern, meaning that there may be carriers with abnormal ……………. and normal …………….. Other predisposed breeds include the British Shorthair, Norwegian Forest Cat, Turkish Van, Scottish fold, Bengal, Siberian, and Rex.

Answer 6

Genetics of Hypertrophic Cardiomyopathy

In people, 66% of HCM cases are due to a familial heritable sarcomeric defect, and the remaining cases are de novo spontaneous mutations. There is a familial heritability in some purebred cats including an autosomal dominant heritability in the Ragdoll cat, Maine Coon cat, and American Shorthair cat. Maine Coon cats have an incomplete penetrance pattern, meaning that there may be carriers with abnormal genotype and normal phenotype. Other predisposed breeds include the British Shorthair, Norwegian Forest Cat, Turkish Van, Scottish fold, Bengal, Siberian, and Rex.

Question 7

Two separate mutations in the cardiac ……………………… (……………………..) gene have been identified to cause HCM in Maine Coon cats and…………… cats. These mutations cause a switch in conserved …………………, which alters the computed structure of ………………. There are likely additional mutations causing HCM in Maine Coon cats, as some cats with phenotypic evidence of HCM do not have the mutation in MYBPC gene. Conversely, cats may carry the mutation of MYBPC gene without having phenotypic evidence of HCM.

Answer 7

Two separate mutations in the cardiac myosin binding protein C (MYBPC) gene have been identified to cause HCM in Maine Coon cats and Ragdoll cats. These mutations cause a switch in conserved amino acids, which alters the computed structure of MYBPC. There are likely additional mutations causing HCM in Maine Coon cats, as some cats with phenotypic evidence of HCM do not have the mutation in MYBPC gene. Conversely, cats may carry the mutation of MYBPC gene without having phenotypic evidence of HCM.

Question 8

PATHOPHYSIOLOGY

The initial abnormality hypothesized to occur in HCM is a ………………. defect at the level of the ……………….., the smallest contractile unit of the cardiomyocyte. Altered sarcomeric mechanical function leads to increased signal transduction of stress responsive intracellular signaling …………, ……………. sensitive signaling molecules, and ………………. factors.

Answer 8

The initial abnormality hypothesized to occur in HCM is a functional defect at the level of the sarcomere, the smallest contractile unit of the cardiomyocyte.[3] Altered sarcomeric mechanical function leads to increased signal transduction of stress responsive intracellular signaling kinases, calcium sensitive signaling molecules, and trophic factors.

Question 9

Transcriptional machinery of the myocyte is activated, which leads to myocyte …………………, ………………… synthesis, and myocyte ………………………

Answer 9

Transcriptional machinery of the myocyte is activated, which leads to myocyte hypertrophy, collagen synthesis, and myocyte disarray.

Question 10

Environmental factors, genetic factors including polymorphisms of renin angiotensin aldosterone system (RAAS), and concomitant disease influence the final phenotype of LV hypertrophy, which is a compensatory change occurring later in disease.

Answer 10

Environmental factors, genetic factors including polymorphisms of renin angiotensin aldosterone system (RAAS), and concomitant disease influence the final phenotype of LV hypertrophy, which is a compensatory change occurring later in disease.

Question 11

Early …………………. relaxation is impaired by altered ……………… handling (i.e., ……………………. ……………… sensitivity of the myofilaments), myocardial ……………….., altered LV …………………., regional myocardial …………………., and ………………….
Delayed or incomplete relaxation not only negatively impacts early …………….., but the continuing interaction of contractile elements and persistent development of myocardial tension increase myocardial ……………………… The LV compliance is reduced (i.e., it becomes more stiff) because of LV concentric hypertrophy, myocardial fibrosis, and myofiber disarray.

Answer 11

Early diastolic relaxation is impaired by altered calcium handling (i.e., increased calcium sensitivity of the myofilaments), myocardial ischemia, altered LV loading, regional myocardial asynchrony, and hypertrophy.

Delayed or incomplete relaxation not only negatively impacts early diastole, but the continuing interaction of contractile elements and persistent development of myocardial tension increase myocardial stiffness. The LV compliance is reduced (i.e., it becomes more stiff) because of LV concentric hypertrophy, myocardial fibrosis, and myofiber disarray.

Question 12

The overall impact is ………………. diastolic filling and ……………… diastolic filling ………………

Answer 12

The overall impact is reduced diastolic filling and increased diastolic filling pressure.

Question 13

Increased LV diastolic pressure is transmitted back to the left atrium and causes left atrial dilation. Left-sided congestive heart failure (CHF) develops once the LV ………….. pressure exceeds ≈………… mm Hg, and is evidenced by pulmonary edema and/or pleural effusion in the cat.

Answer 13

Increased LV diastolic pressure is transmitted back to the left atrium and causes left atrial dilation. Left-sided congestive heart failure (CHF) develops once the LV diastolic pressure exceeds ≈25 mm Hg, and is evidenced by pulmonary edema and/or pleural effusion in the cat.

Question 14

Systolic Anterior Motion of the Mitral Valve

Systolic anterior motion (SAM) of the mitral valve is a pathognomic feature of HCM and creates a dynamic obstruction of the anterior mitral leaflet in the left ventricular outflow tract (LVOT). The dynamic obstruction worsens through systole and during higher contractile states. The cause of SAM has been debated, but most evidence suggests that it is due to hypertrophied, …………displaced papillary muscles that pull the chordae tendineae and the anterior mitral leaflet into the LVOT to approach or contact the interventricular septum during systole.
Basilar septal hypertrophy also may contribute to SAM of the mitral valve. Significant LVOT obstruction increases LV ………………. pressure and worsens hypertrophy. In addition to LVOT obstruction, SAM of the mitral valve causes mitral regurgitation, which further increases left atrial pressure and dilation.

Answer 14

Systolic Anterior Motion of the Mitral Valve

Systolic anterior motion (SAM) of the mitral valve is a pathognomic feature of HCM and creates a dynamic obstruction of the anterior mitral leaflet in the left ventricular outflow tract (LVOT). The dynamic obstruction worsens through systole and during higher contractile states. The cause of SAM has been debated, but most evidence suggests that it is due to hypertrophied, anteriorly displaced papillary muscles that pull the chordae tendineae and the anterior mitral leaflet into the LVOT to approach or contact the interventricular septum during systole.
Basilar septal hypertrophy also may contribute to SAM of the mitral valve. Significant LVOT obstruction increases LV systolic pressure and worsens hypertrophy. In addition to LVOT obstruction, SAM of the mitral valve causes mitral regurgitation, which further increases left atrial pressure and dilation.

Question 15

Arterial Thromboembolism

HCM is the most common cardiac disease in cats suffering from arterial thromboembolism (ATE), probably because it is the most common feline cardiomyopathy. The incidence of ATE in cats with HCM is 16% to 18%. Left atrial dilation is necessary for development of cardiogenic ATE in cats. In one study of ATE in cats, the left atrium was severely enlarged in 57%, moderately enlarged in 14%, and mildly enlarged in 22%, with only 5% having a normal left atrial size.[7]

Thrombus formation may develop when there is an abnormality in one or more of the components of Virchow’s triangle, which includes ………………, ……………….., ……………….

Answer 15

Arterial Thromboembolism

HCM is the most common cardiac disease in cats suffering from arterial thromboembolism (ATE), probably because it is the most common feline cardiomyopathy. The incidence of ATE in cats with HCM is 16% to 18%. Left atrial dilation is necessary for development of cardiogenic ATE in cats. In one study of ATE in cats, the left atrium was severely enlarged in 57%, moderately enlarged in 14%, and mildly enlarged in 22%, with only 5% having a normal left atrial size.[7]

Thrombus formation may develop when there is an abnormality in one or more of the components of Virchow’s triangle, which includes hypercoagulability, endothelial disruption, and blood stasis.

Question 16

When the left atrium becomes moderately to severely dilated, the blood flow velocity is …………., resulting in red cell ……………, platelet ……………, and thrombus ……………. Left auricular blood flow velocity was shown to be reduced in cats with echocardiographic evidence of spontaneous contrast and red blood cell aggregation.[8] Similarly, half of cats with cardiomyopathy and echocardiographic evidence of spontaneous contrast have evidence of hypercoagulability.[9]

Answer 16

When the left atrium becomes moderately to severely dilated, the blood flow velocity is reduced, resulting in red cell aggregation, platelet activation, and thrombus formation. Left auricular blood flow velocity was shown to be reduced in cats with echocardiographic evidence of spontaneous contrast and red blood cell aggregation.[8] Similarly, half of cats with cardiomyopathy and echocardiographic evidence of spontaneous contrast have evidence of hypercoagulability.[9]

Question 17

A recent study documented that 45% of asymptomatic cats with HCM had evidence of hypercoagulability.[10] It is debatable whether there is platelet hyperreactivity in cats with cardiac disease because some studies document increased platelet reactivity and others report no change in platelet function in cats with heart disease.[11-13]

Answer 17

A recent study documented that 45% of asymptomatic cats with HCM had evidence of hypercoagulability.[10] It is debatable whether there is platelet hyperreactivity in cats with cardiac disease because some studies document increased platelet reactivity and others report no change in platelet function in cats with heart disease.[11-13]

Question 18

Endothelial damage and disruption likely occur in cats with cardiac disease, and endothelial damage and fibrin adherence to the subendothelium have been documented on pathologic examination in several cats with CHF.[14]

Answer 18

Endothelial damage and disruption likely occur in cats with cardiac disease, and endothelial damage and fibrin adherence to the subendothelium have been documented on pathologic examination in several cats with CHF.[14]

Question 19

It is likely that a combination of mechanisms leads to development of a left atrial thrombus in cats with significant cardiac disease. Once the thrombus becomes dislodged from the left atrium, it travels through the arterial blood system and becomes lodged in an artery depending on the size of the thrombus, with the most common location the aortic trifurcation (71%) and then the right subclavian–right thoracic limb. More important than the physical obstruction of blood flow in the artery, the thrombus releases vasoactive amines including ……………. and ………………, which cause massive ……………………. of the ……………………arteries, leading to lack of perfusion to the limb.

Answer 19

It is likely that a combination of mechanisms leads to development of a left atrial thrombus in cats with significant cardiac disease. Once the thrombus becomes dislodged from the left atrium, it travels through the arterial blood system and becomes lodged in an artery depending on the size of the thrombus, with the most common location the aortic trifurcation (71%) and then the right subclavian–right thoracic limb. More important than the physical obstruction of blood flow in the artery, the thrombus releases vasoactive amines including thromboxane and serotonin, which cause massive vasoconstriction of the collateral arteries, leading to lack of perfusion to the limb.

Question 20

PATHOLOGY

Concentric hypertrophy of the LV ………….., inter ventricular ……………., and ………….. is grossly evident on pathologic examination (Figure 252-1). Postmortem measurement of wall thickness reflects an end-…….. phase due to rigor mortis. Absolute and relative heart weight is increased in cats with HCM that die of their disease compared with normal cats (29 to 37 g [HCM] versus 6.4 g/kg [HCM] versus

Answer 20

PATHOLOGY

Concentric hypertrophy of the LV free wall, interventricular septum, and papillary muscles is grossly evident on pathologic examination (Figure 252-1). Postmortem measurement of wall thickness reflects an end-systolic phase due to rigor mortis. Absolute and relative heart weight is increased in cats with HCM that die of their disease compared with normal cats (29 to 37 g [HCM] versus 6.4 g/kg [HCM] versus

Question 21

Figure 252-1 Gross pathologic examination of a Maine Coon cat dying from severe hypertrophic cardiomyopathy. There is severe diffuse concentric hypertrophy of the left ventricular free wall, interventricular septum, and papillary muscles. Left atrial dilation is present. There is a fibrotic plaque of the midinterventricular septum where the hypertrophied papillary muscle contacts the septum.

Answer 21

Figure 252-1 Gross pathologic examination of a Maine Coon cat dying from severe hypertrophic cardiomyopathy. There is severe diffuse concentric hypertrophy of the left ventricular free wall, interventricular septum, and papillary muscles. Left atrial dilation is present. There is a fibrotic plaque of the midinterventricular septum where the hypertrophied papillary muscle contacts the septum.

Question 22

The hallmark histopathologic abnormality of HCM is …………….., which is identified as malaligned cardiomyocytes that are oriented perpendicular or obliquely to each other, forming tangled patterns or pinwheel configurations. Myofiber disarray was present in all Maine Coon cats that died from HCM in one study, but in only 30% of domestic short-hair cats with HCM in another study.[15],[17] Interstitial and replacement …………… are also common in cats with HCM. Replacement fibrosis is a reparative process that occurs in regions of myocardial necrosis. Interstitial fibrosis occurs in a more fine, reticulated pattern within the myocardium and likely develops secondary to deleterious myocardial effects of neurohormones including ………………… and ……………………. In addition to myocardial necrosis, cell death may also occur by …………………….. Apoptosis was seen in almost one fifth of the cardiomyocytes in LV endomyocardial biopsies in people with HCM in one study.[18]

Answer 22

The hallmark histopathologic abnormality of HCM is myofiber disarray, which is identified as malaligned cardiomyocytes that are oriented perpendicular or obliquely to each other, forming tangled patterns or pinwheel configurations. Myofiber disarray was present in all Maine Coon cats that died from HCM in one study, but in only 30% of domestic short-hair cats with HCM in another study.[15],[17] Interstitial and replacement fibrosis are also common in cats with HCM. Replacement fibrosis is a reparative process that occurs in regions of myocardial necrosis. Interstitial fibrosis occurs in a more fine, reticulated pattern within the myocardium and likely develops secondary to deleterious myocardial effects of neurohormones including angiotensin II and aldosterone. In addition to myocardial necrosis, cell death may also occur by apoptosis. Apoptosis was seen in almost one fifth of the cardiomyocytes in LV endomyocardial biopsies in people with HCM in one study.[18]

Question 23

Myocardial ischemia is often present in people with HCM, and most likely occurs in cats with HCM. A majority of people (66%) and cats (74%) with HCM have histopathologic evidence of abnormal intramural coronary arteries.[15,17,19] In cats, the arteriolar wall is thickened due to increased …………………. tissue in the intima and media layers. Intramural ……………………. artery disease leads to decreased perfusion of the myocardium and may lead to myocardial necrosis and replacement fibrosis. In fact, moderate to severe myocardial fibrosis was found in regions of small artery disease in people and cats with HCM, implying a probable causal relationship among small artery disease, myocardial ischemia, and necrosis, followed by replacement fibrosis. There is also a reduction in myocardial capillary density in the presence of concentric hypertrophy, which decreases myocardial perfusion.

Answer 23

Myocardial ischemia is often present in people with HCM, and most likely occurs in cats with HCM. A majority of people (66%) and cats (74%) with HCM have histopathologic evidence of abnormal intramural coronary arteries.[15,17,19] In cats, the arteriolar wall is thickened due to increased connective tissue in the intima and media layers. Intramural coronary artery disease leads to decreased perfusion of the myocardium and may lead to myocardial necrosis and replacement fibrosis. In fact, moderate to severe myocardial fibrosis was found in regions of small artery disease in people and cats with HCM, implying a probable causal relationship among small artery disease, myocardial ischemia, and necrosis, followed by replacement fibrosis. There is also a reduction in myocardial capillary density in the presence of concentric hypertrophy, which decreases myocardial perfusion.

Question 24

Patient History and Clinical Abnormalities

A large percentage of cats diagnosed with HCM are asymptomatic (33% to 55%) and are diagnosed by echocardiographic workup of a murmur or gallop heart sound. A murmur is present in most (64% to 72%) cats with HCM.[2],[20] The murmur is typically a left parasternal holosystolic dynamic murmur, which increases as heart rate and contractility increase. The murmur is caused by SAM of the mitral valve with dynamic LVOT obstruction and mitral regurgitation. A gallop is less frequently auscultated (33%), and an arrhythmia is uncommon (7%).[2],[20] A small percentage (5%) of cats have no clinical abnormalities.
Heart failure is present in one third to one half of cats with HCM, which typically present with a history of tachypnea, dyspnea, possible cough/vomiting, and lethargy.[2],[20] Half of cats diagnosed with heart failure had identifiable precipitating events, including fluid administration, anesthesia and surgery, or recent corticosteroid administration 1 to 2 weeks prior to heart failure development.[20]

Answer 24

Patient History and Clinical Abnormalities

A large percentage of cats diagnosed with HCM are asymptomatic (33% to 55%) and are diagnosed by echocardiographic workup of a murmur or gallop heart sound. A murmur is present in most (64% to 72%) cats with HCM.[2],[20] The murmur is typically a left parasternal holosystolic dynamic murmur, which increases as heart rate and contractility increase. The murmur is caused by SAM of the mitral valve with dynamic LVOT obstruction and mitral regurgitation. A gallop is less frequently auscultated (33%), and an arrhythmia is uncommon (7%).[2],[20] A small percentage (5%) of cats have no clinical abnormalities.
Heart failure is present in one third to one half of cats with HCM, which typically present with a history of tachypnea, dyspnea, possible cough/vomiting, and lethargy.[2],[20] Half of cats diagnosed with heart failure had identifiable precipitating events, including fluid administration, anesthesia and surgery, or recent corticosteroid administration 1 to 2 weeks prior to heart failure development.[20]

Question 25

Thoracic Radiographs Cats with mild HCM most often have unremarkable thoracic radiographs with no appreciable cardiomegaly. Cardiomegaly is the most common radiographic abnormality in cats with significant HCM. Vertebral heart scale can be calculated to quantify heart size and determine whether there is cardiomegaly (normal = 7.5 ± 0.3 vertebrae).[21] Left atrial dilation is typically best viewed in the dorsoventral or ventrodorsal view and creates the classic “valentine”-shaped heart (Figure 252-2, B). Pulmonary edema is more common than pleural effusion in cats with heart failure and is seen in 23% to 66% of cats with HCM (Figure 252-2, A). Dyspnea was attributed to pulmonary edema in 80% of cats with HCM, compared with only 14% of cats that were dyspneic from pleural effusion.[20] There is no classic pattern of pulmonary edema formation in cats, unlike the perihilar to caudodorsal distribution of pulmonary edema in dogs with heart failure. Sometimes there is a combination of pulmonary edema and pleural effusion, which makes evaluation of the heart size challenging. Dorsal deviation of the trachea in cats with pleural effusion is not specific for cardiomegaly and may occur as a consequence of the severe pleural effusion.[22] It is important to obtain thoracic radiographs in cats with echocardiographic evidence of left atrial dilation because some of these cats may have heart failure. Follow-up radiographs are essential for assessment of response to pharmacologic therapy in cats with heart failure, and they aid in titration of diuretic dose.

Answer 25

Thoracic Radiographs Cats with mild HCM most often have unremarkable thoracic radiographs with no appreciable cardiomegaly. Cardiomegaly is the most common radiographic abnormality in cats with significant HCM. Vertebral heart scale can be calculated to quantify heart size and determine whether there is cardiomegaly (normal = 7.5 ± 0.3 vertebrae).[21] Left atrial dilation is typically best viewed in the dorsoventral or ventrodorsal view and creates the classic “valentine”-shaped heart (Figure 252-2, B). Pulmonary edema is more common than pleural effusion in cats with heart failure and is seen in 23% to 66% of cats with HCM (Figure 252-2, A). Dyspnea was attributed to pulmonary edema in 80% of cats with HCM, compared with only 14% of cats that were dyspneic from pleural effusion.[20] There is no classic pattern of pulmonary edema formation in cats, unlike the perihilar to caudodorsal distribution of pulmonary edema in dogs with heart failure. Sometimes there is a combination of pulmonary edema and pleural effusion, which makes evaluation of the heart size challenging. Dorsal deviation of the trachea in cats with pleural effusion is not specific for cardiomegaly and may occur as a consequence of the severe pleural effusion.[22] It is important to obtain thoracic radiographs in cats with echocardiographic evidence of left atrial dilation because some of these cats may have heart failure. Follow-up radiographs are essential for assessment of response to pharmacologic therapy in cats with heart failure, and they aid in titration of diuretic dose.

Question 26

Electrocardiogram The electrocardiogram is insensitive for diagnosis of HCM. Increased QRS amplitude of > 0.9 mv may indicate LV hypertrophy but is only present in 12% to 25% of cats with HCM.[2],[23] Left axis deviation (0 degrees to minus 90 degrees) suggestive of left anterior fascicular block or LV enlargement is another relatively common finding in 10% to 33% of cats with HCM.[24],[25] Ventricular premature complexes are the most common arrhythmia in cats with HCM (41%), followed by ventricular tachycardia, atrial premature complexes, atrial tachycardia, or atrial fibrillation. Although uncommon, third-degree atrioventricular block may be seen.

Answer 26

The electrocardiogram is insensitive for diagnosis of HCM. Increased QRS amplitude of > 0.9 mv may indicate LV hypertrophy but is only present in 12% to 25% of cats with HCM.[2],[23] Left axis deviation (0 degrees to minus 90 degrees) suggestive of left anterior fascicular block or LV enlargement is another relatively common finding in 10% to 33% of cats with HCM.[24],[25] Ventricular premature complexes are the most common arrhythmia in cats with HCM (41%), followed by ventricular tachycardia, atrial premature complexes, atrial tachycardia, or atrial fibrillation. Although uncommon, third-degree atrioventricular block may be seen.

Question 27

Echocardiogram The echocardiogram is the essential tool for diagnosis of HCM. HCM is diagnosed by presence of LV concentric hypertrophy defined as an LV free wall or interventricular septal thickness at end-diastole of 6 mm or greater (see Table 252-1). Although there is not a formalized definition of mild, moderate, and severe concentric hypertrophy, the author typically classifies 6 to 6.9 mm as mild, 7 to 7.5 mm as moderate, and >7.5 as severe concentric hypertrophy. There is an equivocal range of 5.5 to 5.9 mm that may be seen in early HCM. Other early changes may include papillary hypertrophy or SAM of the mitral valve. End-systolic cavity obliteration may be seen secondary to LV concentric hypertrophy but may also be seen in severely underloaded dehydrated cats. Increased LV wall thickness reduces systolic wall stress, which can result in hyperdynamic contractions, decreased end-systolic diameter, and increased fractional shortening.

Answer 27

Echocardiogram The echocardiogram is the essential tool for diagnosis of HCM. HCM is diagnosed by presence of LV concentric hypertrophy defined as an LV free wall or interventricular septal thickness at end-diastole of 6 mm or greater (see Table 252-1). Although there is not a formalized definition of mild, moderate, and severe concentric hypertrophy, the author typically classifies 6 to 6.9 mm as mild, 7 to 7.5 mm as moderate, and >7.5 as severe concentric hypertrophy. There is an equivocal range of 5.5 to 5.9 mm that may be seen in early HCM. Other early changes may include papillary hypertrophy or SAM of the mitral valve. End-systolic cavity obliteration may be seen secondary to LV concentric hypertrophy but may also be seen in severely underloaded dehydrated cats. Increased LV wall thickness reduces systolic wall stress, which can result in hyperdynamic contractions, decreased end-systolic diameter, and increased fractional shortening.

Question 28

Measurement of LV wall thickness can be done using two-dimensional echocardiography or M-mode echocardiography in the right parasternal short-axis view at the level of the papillary muscles (Figure 252-3). Measurements made by two-dimensional echocardiography may be more sensitive and accurate than measurements made by M-mode in cases of segmental hypertrophy. In cats with focal basilar septal hypertrophy, the right parasternal long axis view may be most useful for measurement of this discrete region of hypertrophy. Regions of replacement fibrosis may be seen as hyperechoic patches in the subendocardium of the left ventricle. A fibrotic plaque may be seen on the basilar interventricular septum where the anterior mitral valve contacts it (i.e., a kissing lesion) in cats with significant SAM of the mitral valve.

Answer 28

Measurement of LV wall thickness can be done using two-dimensional echocardiography or M-mode echocardiography in the right parasternal short-axis view at the level of the papillary muscles (Figure 252-3). Measurements made by two-dimensional echocardiography may be more sensitive and accurate than measurements made by M-mode in cases of segmental hypertrophy. In cats with focal basilar septal hypertrophy, the right parasternal long axis view may be most useful for measurement of this discrete region of hypertrophy. Regions of replacement fibrosis may be seen as hyperechoic patches in the subendocardium of the left ventricle. A fibrotic plaque may be seen on the basilar interventricular septum where the anterior mitral valve contacts it (i.e., a kissing lesion) in cats with significant SAM of the mitral valve.

Question 29

Left atrial size is most commonly measured in the right parasternal short axis view of the heart base, at the level of the aortic valve (see Figure 252-3). The first frame of aortic valve closure is chosen, and the diameter of the aorta and the body of the left atrium are measured using two-dimensional echocardiography or M-mode echocardiography. The ratio of left atrial diameter to aortic diameter (LA : Ao) is used to eliminate the influence of body size on left atrial size and provides a dimensionless index of atrial size. M-mode measurement may be limited by the angle of the cursor, and left atrial size may be underestimated if the cursor bisects the left auricle rather than the body of the left atrium. Measurements of LA : Ao made by two-dimensional echocardiography are not interchangeable with those made by M-mode.[26] In a study of 17 healthy cats, normal two-dimensional–derived LA : Ao was 1.18 ± 0.11.26 LA : Ao ratio of >1.5 is consistent with left atrial dilation.[26] Normal M-mode–derived LA : Ao in cats is 1.25 ± 0.18 with 95% confidence interval of 1.21 to 1.29.[27] Degree of left atrial dilation is usually a subjective finding, and exact cut-off values for mild, moderate, and severe left atrial dilation have not been formalized, but suggestive cutoffs are 1.51 to 1.79, 1.8 to 2.0, and >2.0, respectively.

Answer 29

Left atrial size is most commonly measured in the right parasternal short axis view of the heart base, at the level of the aortic valve (see Figure 252-3). The first frame of aortic valve closure is chosen, and the diameter of the aorta and the body of the left atrium are measured using two-dimensional echocardiography or M-mode echocardiography. The ratio of left atrial diameter to aortic diameter (LA : Ao) is used to eliminate the influence of body size on left atrial size and provides a dimensionless index of atrial size. M-mode measurement may be limited by the angle of the cursor, and left atrial size may be underestimated if the cursor bisects the left auricle rather than the body of the left atrium. Measurements of LA : Ao made by two-dimensional echocardiography are not interchangeable with those made by M-mode.[26] In a study of 17 healthy cats, normal two-dimensional–derived LA : Ao was 1.18 ± 0.11.26 LA : Ao ratio of >1.5 is consistent with left atrial dilation.[26] Normal M-mode–derived LA : Ao in cats is 1.25 ± 0.18 with 95% confidence interval of 1.21 to 1.29.[27] Degree of left atrial dilation is usually a subjective finding, and exact cut-off values for mild, moderate, and severe left atrial dilation have not been formalized, but suggestive cutoffs are 1.51 to 1.79, 1.8 to 2.0, and >2.0, respectively.

Question 30

Left atrial dilation occurs when there is significant diastolic dysfunction and elevated LV diastolic filling pressures. It is essential to determine whether there is left atrial enlargement in cats with pulmonary infiltrates or pleural effusion because left heart failure can be ruled out if the left atrial size is normal. Spontaneous contrast (i.e., a smoky appearance to the blood) or a left atrial thrombus may be present and is an ominous sign of future ATE (see Figure 252-3

Answer 30

Left atrial dilation occurs when there is significant diastolic dysfunction and elevated LV diastolic filling pressures. It is essential to determine whether there is left atrial enlargement in cats with pulmonary infiltrates or pleural effusion because left heart failure can be ruled out if the left atrial size is normal. Spontaneous contrast (i.e., a smoky appearance to the blood) or a left atrial thrombus may be present and is an ominous sign of future ATE (see Figure 252-3

Question 31

SAM of the mitral valve is a hallmark abnormality seen in some cats with HCM. The right parasternal long axis LVOT view is the most useful view to evaluate for SAM of the mitral valve. Using two-dimensional echocardiography, the anterior leaflet of the mitral valve is seen being pulled by the chordae tendineae into the LVOT during systole, and often contacts the interventricular septum (Figure 252-4, A). SAM of the mitral valve is clearly identified by color flow Doppler, which reveals a double turbulent jet of mitral regurgitation and LVOT obstruction originating from the same point in the LVOT (Figure 252-4, B). The severity of mitral regurgitation may range from trivial to moderate. Using the left apical five-chamber view, continuous wave Doppler is used to measure the velocity of aortic blood flow and quantifies the severity of obstruction. The modified Bernoulli equation (pressure gradient = 4 × velocity2) is used to calculate the LV to aortic pressure gradient and determine the severity of obstruction (mild 80 mm Hg). The obstruction is dynamic and worsens through systole, and it creates a characteristic shape of a “dagger” on continuous wave Doppler interrogation, with a peak velocity at end systole (Figure 252-4, C).

Answer 31

SAM of the mitral valve is a hallmark abnormality seen in some cats with HCM. The right parasternal long axis LVOT view is the most useful view to evaluate for SAM of the mitral valve. Using two-dimensional echocardiography, the anterior leaflet of the mitral valve is seen being pulled by the chordae tendineae into the LVOT during systole, and often contacts the interventricular septum (Figure 252-4, A). SAM of the mitral valve is clearly identified by color flow Doppler, which reveals a double turbulent jet of mitral regurgitation and LVOT obstruction originating from the same point in the LVOT (Figure 252-4, B). The severity of mitral regurgitation may range from trivial to moderate. Using the left apical five-chamber view, continuous wave Doppler is used to measure the velocity of aortic blood flow and quantifies the severity of obstruction. The modified Bernoulli equation (pressure gradient = 4 × velocity2) is used to calculate the LV to aortic pressure gradient and determine the severity of obstruction (mild 80 mm Hg). The obstruction is dynamic and worsens through systole, and it creates a characteristic shape of a “dagger” on continuous wave Doppler interrogation, with a peak velocity at end systole (Figure 252-4, C).

Question 32

Figure 252-4 Echocardiographic assessment of systolic anterior motion of the mitral valve in a cat with severe hypertrophic obstructive cardiomyopathy. This is a magnified view of the anterior mitral valve from the right parasternal long axis left ventricular outflow tract view and shows systolic anterior motion of the mitral valve (A). There are hypertrophied, anteriorly displaced papillary muscles that pull the chordae tendineae and the anterior leaflet toward the severely hypertrophied basilar interventricular septum. Color flow Doppler of the left ventricular outflow tract shows a double turbulent jet where the anterior mitral leaflet obstructs the left ventricular outflow tract and also creates mitral regurgitation (B). From the left apical five-chamber view, continuous wave Doppler is used to measure the aortic blood flow velocity, which is 4 m/s (C). Using the modified Bernoulli equation, there is a 64 mm Hg pressure difference between the left ventricle (LV) and aorta (AO), indicating a moderate obstruction from systolic anterior motion of the mitral valve. LA, Left atrium.

Answer 32

Figure 252-4 Echocardiographic assessment of systolic anterior motion of the mitral valve in a cat with severe hypertrophic obstructive cardiomyopathy. This is a magnified view of the anterior mitral valve from the right parasternal long axis left ventricular outflow tract view and shows systolic anterior motion of the mitral valve (A). There are hypertrophied, anteriorly displaced papillary muscles that pull the chordae tendineae and the anterior leaflet toward the severely hypertrophied basilar interventricular septum. Color flow Doppler of the left ventricular outflow tract shows a double turbulent jet where the anterior mitral leaflet obstructs the left ventricular outflow tract and also creates mitral regurgitation (B). From the left apical five-chamber view, continuous wave Doppler is used to measure the aortic blood flow velocity, which is 4 m/s (C). Using the modified Bernoulli equation, there is a 64 mm Hg pressure difference between the left ventricle (LV) and aorta (AO), indicating a moderate obstruction from systolic anterior motion of the mitral valve. LA, Left atrium.

Question 33

Assessment of Diastolic Function Pulsed wave (PW) Doppler measurement of mitral inflow velocity from the left apical four-chamber view often shows a .............. pattern (early diastolic filling wave [E] to atrial systole [A] wave ratio of

Answer 33

Assessment of Diastolic Function Pulsed wave (PW) Doppler measurement of mitral inflow velocity from the left apical four-chamber view often shows a delayed relaxation pattern (early diastolic filling wave [E] to atrial systole [A] wave ratio of

Question 34

Delayed relaxation is the first level of ............... dysfunction, when there is impaired .................. filling but normal left atrial pressures. As diastolic dysfunction worsens, left .................pressure increases, leading to a ................. filling pattern on mitral inflow velocity measurement. A .................. filling pattern may be seen in cats with severe diastolic dysfunction and severely elevated left .................... and is evidenced by E:A >....., .............deceleration time, and .............. IVRT.

Answer 34

Delayed relaxation is the first level of diastolic dysfunction, when there is impaired early diastolic filling but normal left atrial pressures. As diastolic dysfunction worsens, left atrial pressure increases, leading to a pseudonormal filling pattern on mitral inflow velocity measurement. A restrictive filling pattern may be seen in cats with severe diastolic dysfunction and severely elevated left atrial pressure and is evidenced by E:A >2, decreased deceleration time, and shortened IVRT.

Question 35

Although widely used as a simple, noninvasive method to assess diastolic function, PW Doppler mitral inflow characteristics are greatly impacted by ............... pressures and the ...................... pressure gradient. Increased left atrial pressure may mask a delayed relaxation pattern. Oppositely, increased heart rate, decreased preload, and increased afterload accentuate a delayed relaxation pattern.[28] There is EA summation in cats with tachycardia typically over 150 beats/min, which prevents assessment of diastolic function by assessment of mitral inflow profiles. Consequently, there has been a search for noninvasive methods to assess diastolic function that are less influenced by alterations in load and can be used in the presence of EA summation.

Answer 35

Although widely used as a simple, noninvasive method to assess diastolic function, PW Doppler mitral inflow characteristics are greatly impacted by filling pressures and the left atrial to LV pressure gradient. Increased left atrial pressure may mask a delayed relaxation pattern. Oppositely, increased heart rate, decreased preload, and increased afterload accentuate a delayed relaxation pattern.[28] There is EA summation in cats with tachycardia typically over 150 beats/min, which prevents assessment of diastolic function by assessment of mitral inflow profiles. Consequently, there has been a search for noninvasive methods to assess diastolic function that are less influenced by alterations in load and can be used in the presence of EA summation.

Question 36

Web Figure 252-1 Delayed relaxation pattern of mitral inflow velocity in a cat with severe hypertrophic cardiomyopathy. This pulsed wave Doppler tracing of mitral inflow velocity indicates a delayed relaxation pattern, with decreased ratio of early (E) to late (A) diastolic filling velocity

Answer 36

Web Figure 252-1 Delayed relaxation pattern of mitral inflow velocity in a cat with severe hypertrophic cardiomyopathy. This pulsed wave Doppler tracing of mitral inflow velocity indicates a delayed relaxation pattern, with decreased ratio of early (E) to late (A) diastolic filling velocity

Question 37

Tissue Doppler Imaging Echocardiography Tissue Doppler imaging (TDI) echocardiography is a useful and sensitive tool to noninvasively assess diastolic and systolic function. It is less sensitive to preload than the traditional method of PW Doppler measurement of mitral inflow.[29-31] Early diastolic velocity of the lateral mitral annulus (Em) reflects global diastolic function of the longitudinal myofibers and may be impaired earlier than the circumferential fibers in cats with HCM.[32] Em measured by PW TDI, color TDI, and peak negative myocardial velocity gradient correlate closely with invasive indices of diastolic function including tau, −dP/dT, and LV end-diastolic pressure in normal people and people with HCM.[33-37] TDI is useful to detect diastolic dysfunction in cats with HCM (Web Figure 252-2).[38-40] Em is often reduced in cats with HCM when compared with normal cats.[38],[41] Normal Em was 12.1 + 2.3 cm/sec in one study, and 8.39 + 2.58 in another study.[38],[41] Em of cats with HCM was lower than normal cats, and reported values included 7.9 + 1.7 cm/sec in one study and 5.24 + 1.22 cm/sec in another study.[38],[41] A cutoff of >7.2 cm/sec is highly sensitive (92%) and specific (87%) for discriminating normal cats from cats with HCM.[41] Other TDI measurements of diastolic function have been shown to be abnormal in cats with HCM including prolonged acceleration and deceleration times of Em and prolonged IVRT.[41]

Answer 37

Tissue Doppler Imaging Echocardiography Tissue Doppler imaging (TDI) echocardiography is a useful and sensitive tool to noninvasively assess diastolic and systolic function. It is less sensitive to preload than the traditional method of PW Doppler measurement of mitral inflow.[29-31] Early diastolic velocity of the lateral mitral annulus (Em) reflects global diastolic function of the longitudinal myofibers and may be impaired earlier than the circumferential fibers in cats with HCM.[32] Em measured by PW TDI, color TDI, and peak negative myocardial velocity gradient correlate closely with invasive indices of diastolic function including tau, −dP/dT, and LV end-diastolic pressure in normal people and people with HCM.[33-37] TDI is useful to detect diastolic dysfunction in cats with HCM (Web Figure 252-2).[38-40] Em is often reduced in cats with HCM when compared with normal cats.[38],[41] Normal Em was 12.1 + 2.3 cm/sec in one study, and 8.39 + 2.58 in another study.[38],[41] Em of cats with HCM was lower than normal cats, and reported values included 7.9 + 1.7 cm/sec in one study and 5.24 + 1.22 cm/sec in another study.[38],[41] A cutoff of >7.2 cm/sec is highly sensitive (92%) and specific (87%) for discriminating normal cats from cats with HCM.[41] Other TDI measurements of diastolic function have been shown to be abnormal in cats with HCM including prolonged acceleration and deceleration times of Em and prolonged IVRT.[41]

Question 38

Web Figure 252-2 Pulsed wave tissue Doppler imaging echocardiography of the lateral mitral annulus of a cat with severe hypertrophic cardiomyopathy. The gate of the pulsed wave Doppler cursor is placed at the lateral mitral annulus from the left apical four-chamber view, and diastolic dysfunction is evidenced by reduced early diastolic mitral annular velocity (Em) and reversal of early to late (A) diastolic velocities. S, Systolic mitral annular velocity.

Answer 38

Web Figure 252-2 Pulsed wave tissue Doppler imaging echocardiography of the lateral mitral annulus of a cat with severe hypertrophic cardiomyopathy. The gate of the pulsed wave Doppler cursor is placed at the lateral mitral annulus from the left apical four-chamber view, and diastolic dysfunction is evidenced by reduced early diastolic mitral annular velocity (Em) and reversal of early to late (A) diastolic velocities. S, Systolic mitral annular velocity.

Question 39

TDI is useful to detect early diastolic dysfunction in people and cats with HCM prior to development of LV hypertrophy. Em was reduced in humans with familial HCM and in transgenic BMHC rabbits with HCM before myocardial hypertrophy developed.[42-47] This early diastolic dysfunction likely reflects mechanical impairment in familial HCM prior to development of the final phenotype of LV hypertrophy.[3] Em is further reduced as diastolic dysfunction progresses and is strongly negatively correlated with amount of increase in LV mass.[42] Using PW TDI, 50% of genotypically affected and phenotypically normal Maine Coon cats had diastolic dysfunction, and cats with abnormal genotype and phenotype had further reductions in Em. Likewise, TDI identified diastolic dysfunction in all carrier cats and affected cats prior to development of concentric hypertrophy in a family of cats with dystrophin-deficient hypertrophic muscular dystrophy

Answer 39

TDI is useful to detect early diastolic dysfunction in people and cats with HCM prior to development of LV hypertrophy. Em was reduced in humans with familial HCM and in transgenic BMHC rabbits with HCM before myocardial hypertrophy developed.[42-47] This early diastolic dysfunction likely reflects mechanical impairment in familial HCM prior to development of the final phenotype of LV hypertrophy.[3] Em is further reduced as diastolic dysfunction progresses and is strongly negatively correlated with amount of increase in LV mass.[42] Using PW TDI, 50% of genotypically affected and phenotypically normal Maine Coon cats had diastolic dysfunction, and cats with abnormal genotype and phenotype had further reductions in Em. Likewise, TDI identified diastolic dysfunction in all carrier cats and affected cats prior to development of concentric hypertrophy in a family of cats with dystrophin-deficient hypertrophic muscular dystrophy

Question 40

Although most cats with HCM appear to have hyperdynamic LV contractions on two-dimensional echocardiography, more subtle systolic abnormalities may be present by TDI measurement of systolic myocardial velocity.[32] Postextrasystolic thickening has been seen in cats with HCM and also indicates systolic dysfunction. Traditional estimates of systolic function such as ejection fraction or fractional shortening reflect global LV chamber function rather than intrinsic myocardial contractility. Possible factors involved in reduced systolic myocardial velocity include subendocardial ischemia, myocyte disarray, heterogeneity of regional wall stress, and myocardial fibrosis.[50]

Answer 40

Although most cats with HCM appear to have hyperdynamic LV contractions on two-dimensional echocardiography, more subtle systolic abnormalities may be present by TDI measurement of systolic myocardial velocity.[32] Postextrasystolic thickening has been seen in cats with HCM and also indicates systolic dysfunction. Traditional estimates of systolic function such as ejection fraction or fractional shortening reflect global LV chamber function rather than intrinsic myocardial contractility. Possible factors involved in reduced systolic myocardial velocity include subendocardial ischemia, myocyte disarray, heterogeneity of regional wall stress, and myocardial fibrosis.[50]

Question 41

Circulating biomarkers Circulating biomarkers have recently gained popularity as noninvasive screening tests for presence of heart disease or heart failure in people, dogs, and cats. Brain natriuretic peptide (BNP) has emerged as a sensitive biomarker for many heart diseases and heart failure. It is normally synthesized in the atria, but in the presence of increased ventricular wall stress and neurohormonal stimulation including endothelin I, there is an increase in ventricular synthesis of BNP. A commercial sandwich ELISA assay for amino terminal probrain natriuretic peptide (NT-proBNP) has been recently validated in cats. It is useful to discriminate heart failure from primary respiratory disease in cats, with a high sensitivity of 94% and a specificity of 86% to 88%.[51],[52] NT-proBNP is also useful to detect cardiomyopathy in asymptomatic cats, with a sensitivity of 88% and specificity of 100% in a small pilot study of 23 cats with various cardiomyopathies.[53] Future larger scale studies will be necessary to further evaluate the many uses of natriuretic peptides as biomarkers for disease, disease progression, prognostic indicators, and for guidance of pharmacologic therapy. Serum cardiac troponin I (cTnI) has also been studied in cats with cardiomyopathy and heart failure and has been shown to be a sensitive biomarker for heart failure in cats (sensitivity 87%, specificity 84%), but it did not distinguish cats that were symptomatic from asymptomatic cats.[54] Another study found contradictory results, with increased cTnI in asymptomatic cats with cardiomyopathy that was further increased in symptomatic cats with heart failure.[55] Normal reference ranges are not interchangeable between the different cTnI sandwich assays.

Answer 41

Circulating biomarkers Circulating biomarkers have recently gained popularity as noninvasive screening tests for presence of heart disease or heart failure in people, dogs, and cats. Brain natriuretic peptide (BNP) has emerged as a sensitive biomarker for many heart diseases and heart failure. It is normally synthesized in the atria, but in the presence of increased ventricular wall stress and neurohormonal stimulation including endothelin I, there is an increase in ventricular synthesis of BNP. A commercial sandwich ELISA assay for amino terminal probrain natriuretic peptide (NT-proBNP) has been recently validated in cats. It is useful to discriminate heart failure from primary respiratory disease in cats, with a high sensitivity of 94% and a specificity of 86% to 88%.[51],[52] NT-proBNP is also useful to detect cardiomyopathy in asymptomatic cats, with a sensitivity of 88% and specificity of 100% in a small pilot study of 23 cats with various cardiomyopathies.[53] Future larger scale studies will be necessary to further evaluate the many uses of natriuretic peptides as biomarkers for disease, disease progression, prognostic indicators, and for guidance of pharmacologic therapy. Serum cardiac troponin I (cTnI) has also been studied in cats with cardiomyopathy and heart failure and has been shown to be a sensitive biomarker for heart failure in cats (sensitivity 87%, specificity 84%), but it did not distinguish cats that were symptomatic from asymptomatic cats.[54] Another study found contradictory results, with increased cTnI in asymptomatic cats with cardiomyopathy that was further increased in symptomatic cats with heart failure.[55] Normal reference ranges are not interchangeable between the different cTnI sandwich assays.

Question 42

Advanced Diagnostic Imaging Cardiac Magnetic Resonance Imaging Cardiac magnetic resonance imaging (cMRI) is the gold standard method to quantify LV mass in people and cats with HCM and is more accurate than echocardiographic quantification of LV mass.[56],[57] Because volumetric data are obtained by cMRI, they are not plagued by geometric assumptions to calculate myocardial mass. The use of cMRI for clinical patients is limited by the requirement of general anesthesia for image acquisition, the high cost, lack of experience in obtaining and analyzing cMRI, and lack of efficient semiautomated image analysis. cMRI is also useful in people to detect presence and extent of myocardial fibrosis, which is evident in 80% of asymptomatic to mildly symptomatic patients with HCM. Assessment of myocardial fibrosis using delayed enhancement (DE) cMRI and calculation of myocardial contrast enhancement has been performed in 26 Maine Coon cats with mild to severe HCM without heart failure and 10 normal control cats.[58] Only one cat with HCM had obvious evidence of DE, and there was no difference in myocardial contrast enhancement between normal cats and cats with HCM. cMRI is an accurate noninvasive tool for assessing left and right ventricular function in people with a wide range of cardiac diseases including DCM, HCM, hypertensive cardiac disease, and aortic stenosis.[59-63]

Answer 42

Advanced Diagnostic Imaging Cardiac Magnetic Resonance Imaging Cardiac magnetic resonance imaging (cMRI) is the gold standard method to quantify LV mass in people and cats with HCM and is more accurate than echocardiographic quantification of LV mass.[56],[57] Because volumetric data are obtained by cMRI, they are not plagued by geometric assumptions to calculate myocardial mass. The use of cMRI for clinical patients is limited by the requirement of general anesthesia for image acquisition, the high cost, lack of experience in obtaining and analyzing cMRI, and lack of efficient semiautomated image analysis. cMRI is also useful in people to detect presence and extent of myocardial fibrosis, which is evident in 80% of asymptomatic to mildly symptomatic patients with HCM. Assessment of myocardial fibrosis using delayed enhancement (DE) cMRI and calculation of myocardial contrast enhancement has been performed in 26 Maine Coon cats with mild to severe HCM without heart failure and 10 normal control cats.[58] Only one cat with HCM had obvious evidence of DE, and there was no difference in myocardial contrast enhancement between normal cats and cats with HCM. cMRI is an accurate noninvasive tool for assessing left and right ventricular function in people with a wide range of cardiac diseases including DCM, HCM, hypertensive cardiac disease, and aortic stenosis.[59-63]

Question 43

Cine cMRI is more sensitive than traditional Doppler echocardiography in detecting diastolic dysfunction in people with LV hypertrophy who have normal mitral inflow Doppler indices of diastolic function.[59] cMRI is also useful in clinical and research settings to serially measure diastolic function before and during pharmacologic treatment.[64],[65] cMRI and PW TDI of the lateral mitral annulus were used to quantify diastolic function in seven Maine Coon cats with moderate to severe HCM without heart failure and in six normal domestic shorthair cats.[66] TDI detected diastolic dysfunction in all cats with HCM, but cMRI derived diastolic variables were not different than normal control cats. It is possible that other cMRI techniques such as velocity-encoded cine MRI or myocardial tagging to calculate strain rate may be more sensitive for detection of diastolic dysfunction.[63,67,68]

Answer 43

Cine cMRI is more sensitive than traditional Doppler echocardiography in detecting diastolic dysfunction in people with LV hypertrophy who have normal mitral inflow Doppler indices of diastolic function.[59] cMRI is also useful in clinical and research settings to serially measure diastolic function before and during pharmacologic treatment.[64],[65] cMRI and PW TDI of the lateral mitral annulus were used to quantify diastolic function in seven Maine Coon cats with moderate to severe HCM without heart failure and in six normal domestic shorthair cats.[66] TDI detected diastolic dysfunction in all cats with HCM, but cMRI derived diastolic variables were not different than normal control cats. It is possible that other cMRI techniques such as velocity-encoded cine MRI or myocardial tagging to calculate strain rate may be more sensitive for detection of diastolic dysfunction.[63,67,68]

Question 44

DIFFERENTIAL DIAGNOSIS Secondary causes of mild concentric hypertrophy of the LV include systemic hypertension, hyperthyroidism, and acromegaly. Fixed subaortic stenosis must also be ruled out as a cause of pressure overload hypertrophy of the LV. Acromegaly is an uncommon disease that causes concentric LV hypertrophy as a result of the direct stimulatory effect of growth hormone on the cardiomyocytes.[69] Doppler blood pressure and thyroxine level must be measured in cats with LV concentric hypertrophy.

Answer 44

DIFFERENTIAL DIAGNOSIS Secondary causes of mild concentric hypertrophy of the LV include systemic hypertension, hyperthyroidism, and acromegaly. Fixed subaortic stenosis must also be ruled out as a cause of pressure overload hypertrophy of the LV. Acromegaly is an uncommon disease that causes concentric LV hypertrophy as a result of the direct stimulatory effect of growth hormone on the cardiomyocytes.[69] Doppler blood pressure and thyroxine level must be measured in cats with LV concentric hypertrophy.

Question 45

Typically secondary causes of concentric hypertrophy lead to mild LV hypertrophy, with wall thickness usually less than 7 mm. Presence of SAM of the mitral valve is a unique abnormality seen in HCM and not in secondary causes of LV hypertrophy, and it aids in distinguishing mild HCM from other secondary causes of hypertrophy. Treatment of secondary causes of LV hypertrophy leads to reduction and typically normalization of the hypertrophy after several months. If secondary causes are resolved and there is persistent hypertrophy, HCM is likely a concurrent problem.

Answer 45

Typically secondary causes of concentric hypertrophy lead to mild LV hypertrophy, with wall thickness usually less than 7 mm. Presence of SAM of the mitral valve is a unique abnormality seen in HCM and not in secondary causes of LV hypertrophy, and it aids in distinguishing mild HCM from other secondary causes of hypertrophy. Treatment of secondary causes of LV hypertrophy leads to reduction and typically normalization of the hypertrophy after several months. If secondary causes are resolved and there is persistent hypertrophy, HCM is likely a concurrent problem.

Question 46

Other causes of increased myocardial thickness are infiltrative neoplasia (i.e., lymphoma) and amyloidosis, which are rare. There is regional hypokinetic wall motion in regions of infiltrative myocardial neoplasia, and often the echotexture is different from the remaining LV myocardium. Mitral valve dysplasia is the main differential for SAM of the mitral valve. Characteristics of mitral valve dysplasia include a thickened mitral valve, with short and thick chordae tendineae. Often the anterior leaflet is elongated and may cause LV outflow obstruction with a similar appearance to SAM of the mitral valve. Unlike mitral valve dysplasia, the mitral valve of cats with SAM is structurally normal but is anteriorly displaced during systole. Fixed subaortic stenosis is another differential for SAM of the mitral valve and is a congenital heart defect. Subaortic stenosis is caused by a fibrotic ring, band, or fibromuscular tunnel in the LV outflow tract just below the aortic cusps and causes LV outflow tract obstruction. Continuous wave Doppler interrogation of aortic blood flow shows a typical fixed obstruction pattern in subaortic stenosis, with a peak systolic velocity during midsystole.

Answer 46

Other causes of increased myocardial thickness are infiltrative neoplasia (i.e., lymphoma) and amyloidosis, which are rare. There is regional hypokinetic wall motion in regions of infiltrative myocardial neoplasia, and often the echotexture is different from the remaining LV myocardium. Mitral valve dysplasia is the main differential for SAM of the mitral valve. Characteristics of mitral valve dysplasia include a thickened mitral valve, with short and thick chordae tendineae. Often the anterior leaflet is elongated and may cause LV outflow obstruction with a similar appearance to SAM of the mitral valve. Unlike mitral valve dysplasia, the mitral valve of cats with SAM is structurally normal but is anteriorly displaced during systole. Fixed subaortic stenosis is another differential for SAM of the mitral valve and is a congenital heart defect. Subaortic stenosis is caused by a fibrotic ring, band, or fibromuscular tunnel in the LV outflow tract just below the aortic cusps and causes LV outflow tract obstruction. Continuous wave Doppler interrogation of aortic blood flow shows a typical fixed obstruction pattern in subaortic stenosis, with a peak systolic velocity during midsystole.

Question 47

TREATMENT Treatment goals in HCM include reduction in LV hypertrophy, improvement in diastolic function, reduction of moderate or severe SAM of the mitral valve, treatment of CHF, and prophylactic anticoagulation therapy in cats with high risk of ATE.

Answer 47

TREATMENT Treatment goals in HCM include reduction in LV hypertrophy, improvement in diastolic function, reduction of moderate or severe SAM of the mitral valve, treatment of CHF, and prophylactic anticoagulation therapy in cats with high risk of ATE.

Question 48

Treatment of Asymptomatic Cats with Hypertrophic Cardiomyopathy There is great controversy whether asymptomatic cats with HCM should be treated, and whether any medications are beneficial early in the course of disease. Similar controversy exists in human medicine. According to the American College of Cardiology Expert Consensus on HCM, treatment of asymptomatic patients to prevent or delay development of symptoms and improve prognosis is debatable and is on an “empiric basis without controlled data to either support or contradict its potential efficacy.”[70] Asymptomatic patients with massive LV hypertrophy are usually treated with expectations that pharmacologic therapy will improve diastolic filling, reduce myocardial ischemia, and prolong time to development of symptoms.[71] Likewise, negative inotropic therapy with either a beta-blocker or calcium channel blocker is typically elected in cats with severe LV hypertrophy (wall thickness ≥7.5 to 8 mm). There is a stark lack of controlled, well-designed studies evaluating effect of different treatments in cats with HCM.

Answer 48

Treatment of Asymptomatic Cats with Hypertrophic Cardiomyopathy There is great controversy whether asymptomatic cats with HCM should be treated, and whether any medications are beneficial early in the course of disease. Similar controversy exists in human medicine. According to the American College of Cardiology Expert Consensus on HCM, treatment of asymptomatic patients to prevent or delay development of symptoms and improve prognosis is debatable and is on an “empiric basis without controlled data to either support or contradict its potential efficacy.”[70] Asymptomatic patients with massive LV hypertrophy are usually treated with expectations that pharmacologic therapy will improve diastolic filling, reduce myocardial ischemia, and prolong time to development of symptoms.[71] Likewise, negative inotropic therapy with either a beta-blocker or calcium channel blocker is typically elected in cats with severe LV hypertrophy (wall thickness ≥7.5 to 8 mm). There is a stark lack of controlled, well-designed studies evaluating effect of different treatments in cats with HCM.

Question 49

Intense debate exists over whether calcium channel blockers or beta-blockers are superior for treatment of patients with HCM. Although beta-blockers worsen ..................., there is symptomatic benefit in slowing the heart rate and prolonging .................. to increase passive LV filling.[70] Negative inotropic effects and reduction of myocardial oxygen demand may reduce microvascular myocardial ................. Beta-blockers are also effective in reducing ..............obstruction, and in cats they are superior to calcium channel blockers at reducing SAM. Calcium channel blockers also reduce symptoms in people with HCM. Calcium channel blockers improve ..................... relaxation by reducing tau and reducing IVRT. Although beta-blockers and calcium channel blockers are commonly used to treat cats with HCM, there is a lack of studies evaluating their effects in this population. A prospective, blinded, placebo-controlled study evaluated the effects of atenolol versus diltiazem in asymptomatic cats with HCM.[74] Results were relatively underwhelming. Atenolol had modest effects of improving one variable of diastolic function, slightly reducing septal thickness, and slightly reducing the severity of SAM. There were no significant effects of diltiazem on diastolic function, left atrial size, LV hypertrophy, or severity of SAM. In contrast, a small, unblinded, uncontrolled study found that diltiazem reduced LV free wall and interventricular septal thickness from 9 mm ± 0.5 mm to 6 mm ± 0.6 mm after 6 months of therapy, improved symptoms, and shortened LV relaxation time index after 3 and 6 months of treatment in 12 cats with HCM.[75

Answer 49

Intense debate exists over whether calcium channel blockers or beta-blockers are superior for treatment of patients with HCM. Although beta-blockers worsen early relaxation, there is symptomatic benefit in slowing the heart rate and prolonging diastole to increase passive LV filling.[70] Negative inotropic effects and reduction of myocardial oxygen demand may reduce microvascular myocardial ischemia. Beta-blockers are also effective in reducing LVOT obstruction, and in cats they are superior to calcium channel blockers at reducing SAM.[72] Calcium channel blockers also reduce symptoms in people with HCM. Calcium channel blockers improve early diastolic relaxation by reducing tau and reducing IVRT.[73] Although beta-blockers and calcium channel blockers are commonly used to treat cats with HCM, there is a lack of studies evaluating their effects in this population. A prospective, blinded, placebo-controlled study evaluated the effects of atenolol versus diltiazem in asymptomatic cats with HCM.[74] Results were relatively underwhelming. Atenolol had modest effects of improving one variable of diastolic function, slightly reducing septal thickness, and slightly reducing the severity of SAM. There were no significant effects of diltiazem on diastolic function, left atrial size, LV hypertrophy, or severity of SAM. In contrast, a small, unblinded, uncontrolled study found that diltiazem reduced LV free wall and interventricular septal thickness from 9 mm ± 0.5 mm to 6 mm ± 0.6 mm after 6 months of therapy, improved symptoms, and shortened LV relaxation time index after 3 and 6 months of treatment in 12 cats with HCM.[75]

Question 50

Pharmacologic antagonism of RAAS has the physiologic goal of reducing the prohypertrophic and profibrotic effects of angiotensin II and aldosterone. Rationale for the use of RAAS antagonists for treatment of HCM is supported by in vitro and in vivo experimental evidence that ACE inhibitors and angiotensin receptor blockers (ARB) prevent angiotensin II or aldosterone-induced LV hypertrophy and myocardial fibrosis.[76-80] Additionally, in a troponin T transgenic mouse model of human HCM, treatment with an angiotensin II receptor blocker reversed myocardial fibrosis but had no effect on myofiber disarray.[81] There are only four studies evaluating RAAS antagonists for treatment of asymptomatic cats with HCM.[82-85] The first study evaluated the effect of ramipril (0.5 mg/kg PO q24h) on LV mass quantified by cMRI, diastolic function quantified by PW TDI, neurohormones including plasma aldosterone and BNP concentrations, and blood pressure in 26 Maine Coon cats with mild to severe familial HCM without CHF.[86] There was no difference in LV mass, diastolic function, delayed contrast enhancement assessment of myocardial fibrosis, blood pressure, or neurohormones between the placebo and ramipril treatment groups over 12 months of therapy. In contradiction, two small, uncontrolled or retrospective studies reported that ACE inhibitors reduced LV hypertrophy assessed by M-mode or two-dimensional echocardiography.[84],[87] However, two-dimensional echocardiographic assessment of hypertrophy is fraught with high interobserver and intraobserver variability of 18% to 20%, respectively. Another study evaluated the effect of spironolactone (2 mg/kg PO bid × 4 months) on diastolic function assessed by TDI, cardiac mass quantified by the truncated ellipse formula using echocardiography, left atrial size, and plasma aldosterone concentration in 26 Maine Coon and Maine Coon cross-bred cats with asymptomatic mild to severe familial HCM and diastolic dysfunction. There was no difference in diastolic function or systolic function assessed by TDI, LV mass, or left atrial size. Serum aldosterone concentration was markedly elevated in cats treated with spironolactone. Approximately one third of cats given spironolactone developed severe facial ulcerative dermatitis, which may have been caused by a drug reaction.

Answer 50

Pharmacologic antagonism of RAAS has the physiologic goal of reducing the prohypertrophic and profibrotic effects of angiotensin II and aldosterone. Rationale for the use of RAAS antagonists for treatment of HCM is supported by in vitro and in vivo experimental evidence that ACE inhibitors and angiotensin receptor blockers (ARB) prevent angiotensin II or aldosterone-induced LV hypertrophy and myocardial fibrosis.[76-80] Additionally, in a troponin T transgenic mouse model of human HCM, treatment with an angiotensin II receptor blocker reversed myocardial fibrosis but had no effect on myofiber disarray.[81] There are only four studies evaluating RAAS antagonists for treatment of asymptomatic cats with HCM.[82-85] The first study evaluated the effect of ramipril (0.5 mg/kg PO q24h) on LV mass quantified by cMRI, diastolic function quantified by PW TDI, neurohormones including plasma aldosterone and BNP concentrations, and blood pressure in 26 Maine Coon cats with mild to severe familial HCM without CHF.[86] There was no difference in LV mass, diastolic function, delayed contrast enhancement assessment of myocardial fibrosis, blood pressure, or neurohormones between the placebo and ramipril treatment groups over 12 months of therapy. In contradiction, two small, uncontrolled or retrospective studies reported that ACE inhibitors reduced LV hypertrophy assessed by M-mode or two-dimensional echocardiography.[84],[87] However, two-dimensional echocardiographic assessment of hypertrophy is fraught with high interobserver and intraobserver variability of 18% to 20%, respectively. Another study evaluated the effect of spironolactone (2 mg/kg PO bid × 4 months) on diastolic function assessed by TDI, cardiac mass quantified by the truncated ellipse formula using echocardiography, left atrial size, and plasma aldosterone concentration in 26 Maine Coon and Maine Coon cross-bred cats with asymptomatic mild to severe familial HCM and diastolic dysfunction. There was no difference in diastolic function or systolic function assessed by TDI, LV mass, or left atrial size. Serum aldosterone concentration was markedly elevated in cats treated with spironolactone. Approximately one third of cats given spironolactone developed severe facial ulcerative dermatitis, which may have been caused by a drug reaction.

Question 51

Congestive Heart Failure Treatment of symptomatic cats with CHF due to diastolic dysfunction is aimed at reducing fluid accumulation with diuretics and ACE inhibitor therapy. However, the largest multicenter study to date did not identify an improved survival in cats with cardiomyopathy and CHF or ATE treated with beta-blockers, calcium channel blockers, or ACEi.[88] The mainstay for heart failure treatment in cats includes furosemide and an angiotensin-converting enzyme inhibitor. Furosemide is well tolerated in cats that are eating and drinking and is highly effective for treatment of CHF. Doses of 1 to 4 mg/kg PO q24h to tid are used in treatment of heart failure in cats, starting at the lowest effective dose. Hydrochlorothiazide (1 to 2 mg/kg PO q24h to bid) may be added for additional diuresis in refractory heart failure cases, with the likelihood of significant but often clinically tolerable azotemia. Baseline urinalysis and serum chemistry is necessary prior to treatment with furosemide and an ACE inhibitor, and a renal panel should be repeated 1 to 2 weeks after starting therapy

Answer 51

Congestive Heart Failure Treatment of symptomatic cats with CHF due to diastolic dysfunction is aimed at reducing fluid accumulation with diuretics and ACE inhibitor therapy. However, the largest multicenter study to date did not identify an improved survival in cats with cardiomyopathy and CHF or ATE treated with beta-blockers, calcium channel blockers, or ACEi.[88] The mainstay for heart failure treatment in cats includes furosemide and an angiotensin-converting enzyme inhibitor. Furosemide is well tolerated in cats that are eating and drinking and is highly effective for treatment of CHF. Doses of 1 to 4 mg/kg PO q24h to tid are used in treatment of heart failure in cats, starting at the lowest effective dose. Hydrochlorothiazide (1 to 2 mg/kg PO q24h to bid) may be added for additional diuresis in refractory heart failure cases, with the likelihood of significant but often clinically tolerable azotemia. Baseline urinalysis and serum chemistry is necessary prior to treatment with furosemide and an ACE inhibitor, and a renal panel should be repeated 1 to 2 weeks after starting therapy

Question 52

Anticoagulant Therapy Prophylactic anticoagulant therapy is indicated for cats with echocardiographic evidence of spontaneous contrast, intracardiac thrombi, or in cats previously suffering from ATE. The incidence of ATE in cats with HCM is 16% to 18%. Anticoagulant choices include low-dose aspirin (5 to 81 mg PO q 3 days), clopidogrel (18.75 mg PO q24h), low-molecular-weight heparin (Lovenox 1.5 mg/kg SC bid to tid), or coumadin. In cats with spontaneous contrast seen by echocardiography, repeat echocardiographic assessment of spontaneous contrast should be done after anticoagulant therapy is started, and combination therapy may be necessary for cats with persistent spontaneous contrast.

Answer 52

Anticoagulant Therapy Prophylactic anticoagulant therapy is indicated for cats with echocardiographic evidence of spontaneous contrast, intracardiac thrombi, or in cats previously suffering from ATE. The incidence of ATE in cats with HCM is 16% to 18%. Anticoagulant choices include low-dose aspirin (5 to 81 mg PO q 3 days), clopidogrel (18.75 mg PO q24h), low-molecular-weight heparin (Lovenox 1.5 mg/kg SC bid to tid), or coumadin. In cats with spontaneous contrast seen by echocardiography, repeat echocardiographic assessment of spontaneous contrast should be done after anticoagulant therapy is started, and combination therapy may be necessary for cats with persistent spontaneous contrast.

Question 53

PROGNOSIS Survival time is highly variable in cats diagnosed with HCM. Young, male purebred cats (especially Ragdoll cats) tend to have more severe disease that is rapidly progressive. Median survival time of cats with HCM surviving more than 24 hours from time of diagnosis was 709 days in one study.[20] Median survival time was 1129 days in asymptomatic cats, 654 days in cats with heart failure, and only 184 days in cats suffering from ATE. As in people, left atrial size and age were negative predictors of survival.

Answer 53

PROGNOSIS Survival time is highly variable in cats diagnosed with HCM. Young, male purebred cats (especially Ragdoll cats) tend to have more severe disease that is rapidly progressive. Median survival time of cats with HCM surviving more than 24 hours from time of diagnosis was 709 days in one study.[20] Median survival time was 1129 days in asymptomatic cats, 654 days in cats with heart failure, and only 184 days in cats suffering from ATE. As in people, left atrial size and age were negative predictors of survival.

Question 54

DILATED CARDIOMYOPATHY DCM is an uncommon feline cardiomyopathy, consisting of a primary .............. myocardial failure. Most cats now develop .......... DCM because the recognition of taurine-induced myocardial failure in 1987 led to commercial feline diets supplemented with adequate taurine concentration.[89]

Answer 54

DILATED CARDIOMYOPATHY DCM is an uncommon feline cardiomyopathy, consisting of a primary systolic myocardial failure. Most cats now develop idiopathic DCM because the recognition of taurine-induced myocardial failure in 1987 led to commercial feline diets supplemented with adequate taurine concentration.[89]

Question 55

The differentials for systolic myocardial failure include...?

Answer 55

Idiopathic DCM, Taurine deficiency–induced cardiomyopathy, tachycardiomyopathy, Severe volume overload leading to secondary myocardial failure (i.e., severe mitral insufficiency or large left-to-right shunting congenital heart diseases), Toxicity such as doxorubicin cardiotoxicity. Idiopathic DCM is a diagnosis of exclusion of other causes of secondary myocardial failure.

Question 56

ETIOLOGY A genetic etiology of DCM has been identified in 20% to 35% of people with DCM, including familial inherited mutations in sarcomeric proteins, mitochondrial proteins, cytoskeletal/sarcolemmal proteins, nuclear envelope proteins, and transcriptional coactivator proteins.[90] The predominant mode of inheritance in people is autosomal dominant and is caused by the same sarcolemmal protein mutations that cause familial HCM, including cardiac actin; tropomyosin; cardiac troponin T, I, and C; and myosin heavy chain, myosin binding protein C, and Z-disc–encoding proteins.[90] No causative mutations have been discovered in familial DCM of Doberman Pinschers or other predisposed breeds. No genetic studies have evaluated possible mutations in feline DCM because it is so rarely diagnosed in cats. Using quantitative genetic evaluation of clinical DCM in a large colony of domestic shorthair cats, there was evidence for genetic involvement, with a complex pattern of inheritance.

Answer 56

ETIOLOGY A genetic etiology of DCM has been identified in 20% to 35% of people with DCM, including familial inherited mutations in sarcomeric proteins, mitochondrial proteins, cytoskeletal/sarcolemmal proteins, nuclear envelope proteins, and transcriptional coactivator proteins.[90] The predominant mode of inheritance in people is autosomal dominant and is caused by the same sarcolemmal protein mutations that cause familial HCM, including cardiac actin; tropomyosin; cardiac troponin T, I, and C; and myosin heavy chain, myosin binding protein C, and Z-disc–encoding proteins.[90] No causative mutations have been discovered in familial DCM of Doberman Pinschers or other predisposed breeds. No genetic studies have evaluated possible mutations in feline DCM because it is so rarely diagnosed in cats. Using quantitative genetic evaluation of clinical DCM in a large colony of domestic shorthair cats, there was evidence for genetic involvement, with a complex pattern of inheritance.

Question 57

HISTORY A prolonged occult phase of DCM has been recognized in dogs and in humans. This occult phase may consist of several years of mild myocardial failure and possible ventricular arrhythmias without overt heart failure symptoms. An occult phase is likely present in cats but is not clinically well described. Typically, cats are diagnosed with DCM at the end-stage phase when they have symptoms referable to heart failure. Often history is nonspecific, and presenting complaints may include: lethargy, anorexia, respiratory abnormalities, exercise intolerance, possible syncope, cough, or vomiting. A thorough dietary history should be obtained to evaluate whether there is likelihood of taurine deficiency (see Taurine Deficiency–Induced Myocardial Failure later).

Answer 57

HISTORY A prolonged occult phase of DCM has been recognized in dogs and in humans. This occult phase may consist of several years of mild myocardial failure and possible ventricular arrhythmias without overt heart failure symptoms. An occult phase is likely present in cats but is not clinically well described. Typically, cats are diagnosed with DCM at the end-stage phase when they have symptoms referable to heart failure. Often history is nonspecific, and presenting complaints may include: lethargy, anorexia, respiratory abnormalities, exercise intolerance, possible syncope, cough, or vomiting. A thorough dietary history should be obtained to evaluate whether there is likelihood of taurine deficiency (see Taurine Deficiency–Induced Myocardial Failure later).

Question 58

Clinical Abnormalities on Physical Examination The most common auscultation abnormalities are gallop heart sound (79%) or a soft left parasternal holosystolic murmur (17%).[92] Most cats diagnosed with DCM suffer from heart failure, with pleural effusion more common than pulmonary edema (91% vs. 36%).[92] Cats usually exhibit tachypnea, dyspnea, and orthopnea, and lung sounds are often muffled. There may be increased adventitious lung sounds in cats with pulmonary edema. Right heart failure may be evident as abdominal distension, hepatomegaly, and jugular venous distension. Femoral arterial pulses are often weak. Mucous membranes are typically normal but may be pale if there is low output heart failure or cardiogenic shock.

Answer 58

The most common auscultation abnormalities are gallop heart sound (79%) or a soft left parasternal holosystolic murmur (17%).[92] Most cats diagnosed with DCM suffer from heart failure, with pleural effusion more common than pulmonary edema (91% vs. 36%).[92] Cats usually exhibit tachypnea, dyspnea, and orthopnea, and lung sounds are often muffled. There may be increased adventitious lung sounds in cats with pulmonary edema. Right heart failure may be evident as abdominal distension, hepatomegaly, and jugular venous distension. Femoral arterial pulses are often weak. Mucous membranes are typically normal but may be pale if there is low output heart failure or cardiogenic shock.

Question 59

Electrocardiogram Arrhythmias are variably present in cats with DCM. The most common arrhythmias are ventricular premature complexes (in 9% to 36% of cases) and supraventricular tachycardia (in 27% to 36% of cases)[1],[2] (Web Figure 252-3). Atrial fibrillation is rarely diagnosed (in 1 of 11 cats in one report) and occurs when there is significant left atrial dilation.[1] Electrocardiography is insensitive for detection of chamber enlargement in cats, and LV enlargement pattern was seen in 2 of 11 cats in one case series.[1] Significant sustained tachyarrhythmias such as supraventricular tachycardia are important to be identified because chronic severe tachycardia may lead to a reversible tachycardiomyopathy characterized by myocardial failure.

Answer 59

Electrocardiogram Arrhythmias are variably present in cats with DCM. The most common arrhythmias are ventricular premature complexes (in 9% to 36% of cases) and supraventricular tachycardia (in 27% to 36% of cases)[1],[2] (Web Figure 252-3). Atrial fibrillation is rarely diagnosed (in 1 of 11 cats in one report) and occurs when there is significant left atrial dilation.[1] Electrocardiography is insensitive for detection of chamber enlargement in cats, and LV enlargement pattern was seen in 2 of 11 cats in one case series.[1] Significant sustained tachyarrhythmias such as supraventricular tachycardia are important to be identified because chronic severe tachycardia may lead to a reversible tachycardiomyopathy characterized by myocardial failure.

Question 60

Thoracic Radiographs Typical radiographic abnormalities seen in cats with DCM are generalized cardiomegaly and atrial dilation (Web Figure 252-4). Radiographs are essential to evaluate for CHF and to assess adequacy of heart failure treatment. Pleural effusion and ascites are more common (91% and 55%, respectively) than pulmonary edema (36%) in one case series.[2]

Answer 60

Thoracic Radiographs Typical radiographic abnormalities seen in cats with DCM are generalized cardiomegaly and atrial dilation (Web Figure 252-4). Radiographs are essential to evaluate for CHF and to assess adequacy of heart failure treatment. Pleural effusion and ascites are more common (91% and 55%, respectively) than pulmonary edema (36%) in one case series.[2]

Question 61

Echocardiogram DCM is defined as a primary myocardial failure, which is diagnosed by a decreased fractional shortening of 11 mm (Figure 252-5, see Table 252-1). There is a secondary compensatory eccentric hypertrophy, which is identified as an increased end-diastolic diameter (>18 mm) (see Figure 252-5).

Answer 61

Echocardiogram DCM is defined as a primary myocardial failure, which is diagnosed by a decreased fractional shortening of 11 mm (Figure 252-5, see Table 252-1). There is a secondary compensatory eccentric hypertrophy, which is identified as an increased end-diastolic diameter (>18 mm) (see Figure 252-5).

Question 62

E-point to septal separation is another index of systolic function and is increased (>4 mm). Left atrial dilation occurs secondary to elevated LV filling pressure and is identified as an LA : Ao >1.5. Other indexes of systolic function may be abnormal and include increased preejection period (PEP), decreased LV ejection time (LVET), increased PEP/LVET, and decreased velocity of circumferential fiber shortening. Systolic dysfunction is evident on TDI as reduced systolic myocardial velocity, and there may also be diastolic dysfunction diagnosed by reduced early diastolic myocardial velocity. Other subjective abnormalities include right ventricular eccentric hypertrophy and myocardial failure and right atrial dilation (see Figure 252-5).

Answer 62

E-point to septal separation is another index of systolic function and is increased (>4 mm). Left atrial dilation occurs secondary to elevated LV filling pressure and is identified as an LA : Ao >1.5. Other indexes of systolic function may be abnormal and include increased preejection period (PEP), decreased LV ejection time (LVET), increased PEP/LVET, and decreased velocity of circumferential fiber shortening. Systolic dysfunction is evident on TDI as reduced systolic myocardial velocity, and there may also be diastolic dysfunction diagnosed by reduced early diastolic myocardial velocity. Other subjective abnormalities include right ventricular eccentric hypertrophy and myocardial failure and right atrial dilation (see Figure 252-5).

Question 63

Mild functional (secondary) atrioventricular valvular insufficiency is also common and occurs secondary to annular dilation and lateralization of the papillary muscles. Spontaneous contrast in the atria may occur secondary to blood stasis. Intraatrial thrombi were identified in 18% of cats in one case series.[2] Mild pericardial effusion is also common but is not so significant as to cause cardiac tamponade.

Answer 63

Mild functional (secondary) atrioventricular valvular insufficiency is also common and occurs secondary to annular dilation and lateralization of the papillary muscles. Spontaneous contrast in the atria may occur secondary to blood stasis. Intraatrial thrombi were identified in 18% of cats in one case series.[2] Mild pericardial effusion is also common but is not so significant as to cause cardiac tamponade.

Question 64

TREATMENT Positive Inotropic Therapy Treatment with positive inotropic drugs including digoxin and pimobendan is indicated for severe myocardial failure and heart failure and is debatable for asymptomatic cats with moderate myocardial failure. Digoxin is a weak positive inotropic agent that also has other effects including increasing vagal tone to slow heart rate, increased respiratory muscle function, enhanced baroreceptor responsiveness, and decreased sympathetic tone. Digoxin dosing is challenging in cats because there is a highly variable half-life of 10 to 79 hours and a narrow therapeutic window of 0.7 to 2 ng/mL. The recommended dose in cats with heart disease or heart failure is 0.007 mg/kg PO q48h, and other doses reported include one fourth of a 0.125 mg tablet orally once a day for cats >4 kg or q48h for cats

Answer 64

TREATMENT Positive Inotropic Therapy Treatment with positive inotropic drugs including digoxin and pimobendan is indicated for severe myocardial failure and heart failure and is debatable for asymptomatic cats with moderate myocardial failure. Digoxin is a weak positive inotropic agent that also has other effects including increasing vagal tone to slow heart rate, increased respiratory muscle function, enhanced baroreceptor responsiveness, and decreased sympathetic tone. Digoxin dosing is challenging in cats because there is a highly variable half-life of 10 to 79 hours and a narrow therapeutic window of 0.7 to 2 ng/mL. The recommended dose in cats with heart disease or heart failure is 0.007 mg/kg PO q48h, and other doses reported include one fourth of a 0.125 mg tablet orally once a day for cats >4 kg or q48h for cats

Question 65

Pimobendan is a powerful inodilator with positive inotropic actions, as well as arteriolar and venodilator activity. The positive inotropic action is through sensitizing troponin C to calcium, as well as by inhibiting phosphodiesterase III degradation of cyclic AMP. It is labeled for treatment of heart failure in dogs and is used off-label in cats for treatment of myocardial failure and heart failure (0.25 mg/kg PO bid).

Answer 65

Pimobendan is a powerful inodilator with positive inotropic actions, as well as arteriolar and venodilator activity. The positive inotropic action is through sensitizing troponin C to calcium, as well as by inhibiting phosphodiesterase III degradation of cyclic AMP. It is labeled for treatment of heart failure in dogs and is used off-label in cats for treatment of myocardial failure and heart failure (0.25 mg/kg PO bid).

Question 66

Antiarrhythmic Therapy Significant ventricular arrhythmias that require treatment include ventricular tachycardia, frequent couplets or triplets, or R on T phenomenon. Because there is minimal contractile reserve in cats with severe myocardial failure, beta-blockers are not likely to be tolerated unless slowly uptitrated over many weeks. This is unrealistic for treatment of significant arrhythmias, so other antiarrhythmic drugs would be preferable. Mexiletine is an oral analog to lidocaine and can be used for treatment of ventricular arrhythmias without causing significant negative inotropic effects (5 mg/kg PO tid). Low-dose sotalol that is uptitrated over a couple of weeks (starting dose 5 to 8 mg PO bid titrate up over 1 to 2 weeks) is another option and can be added to mexiletine for refractory arrhythmias. Supraventricular tachycardia or atrial fibrillation with a rapid ventricular response rate can be treated with diltiazem (7.5 to 15 mg PO tid) and digoxin may be added for additional negative chronotropic effects. Target heart rate is

Answer 66

Antiarrhythmic Therapy Significant ventricular arrhythmias that require treatment include ventricular tachycardia, frequent couplets or triplets, or R on T phenomenon. Because there is minimal contractile reserve in cats with severe myocardial failure, beta-blockers are not likely to be tolerated unless slowly uptitrated over many weeks. This is unrealistic for treatment of significant arrhythmias, so other antiarrhythmic drugs would be preferable. Mexiletine is an oral analog to lidocaine and can be used for treatment of ventricular arrhythmias without causing significant negative inotropic effects (5 mg/kg PO tid). Low-dose sotalol that is uptitrated over a couple of weeks (starting dose 5 to 8 mg PO bid titrate up over 1 to 2 weeks) is another option and can be added to mexiletine for refractory arrhythmias. Supraventricular tachycardia or atrial fibrillation with a rapid ventricular response rate can be treated with diltiazem (7.5 to 15 mg PO tid) and digoxin may be added for additional negative chronotropic effects. Target heart rate is

Question 67

PROGNOSIS Prognosis for idiopathic DCM and heart failure is grave, with a median survival time of 11 days in one case series of 11 cats.[2] Prognosis for taurine deficiency–induced DCM is good as long as the cat survives the first 3 weeks of therapy (see following section). Progressive left- and right-sided heart failure

Answer 67

PROGNOSIS Prognosis for idiopathic DCM and heart failure is grave, with a median survival time of 11 days in one case series of 11 cats.[2] Prognosis for taurine deficiency–induced DCM is good as long as the cat survives the first 3 weeks of therapy (see following section). Progressive left- and right-sided heart failure

Question 68

Taurine Deficiency–Induced Myocardial Failure In 1987, a reversible myocardial failure was recognized in cats associated with low plasma taurine. Prior to this discovery, prognosis of cats with DCM was grave. Taurine is an essential ..........-containing .......... in cats, and has an obligatory role in .............. conjugation.

Answer 68

Taurine Deficiency–Induced Myocardial Failure In 1987, a reversible myocardial failure was recognized in cats associated with low plasma taurine. Prior to this discovery, prognosis of cats with DCM was grave. Taurine is an essential sulfur-containing amino acid in cats, and has an obligatory role in bile salt conjugation.

Question 69

Taurine is synthesized by the ......... and .......... from dietary sulfur amino acids (.............), and the rate of synthesis in the cat is much lower than its loss through .................... of ..................

Answer 69

Taurine is synthesized by the liver and brain from dietary sulfur amino acids (cysteine), and the rate of synthesis in the cat is much lower than its loss through conjugation of cholic acid.

Question 70

Taurine homeostasis in cats depends on .......... intake, ..............synthesis, ................... turnover, microbial .................. in the large intestine, and ................. and fecal losses.

Answer 70

Taurine homeostasis in cats depends on dietary intake, endogenous synthesis, enterohepatic turnover, microbial degradation in the large intestine, and urinary and fecal losses.

Question 71

The minimal dietary concentration of taurine required to maintain normal taurine levels in cats depends on the type of diet. In dry cat food, 1200 mg taurine/kg is adequate, but higher concentration (2500 mg taurine/kg dry matter) is required for canned foods because the heating during canning produces products that increase enterohepatic taurine loss or decrease taurine absorption.

Answer 71

The minimal dietary concentration of taurine required to maintain normal taurine levels in cats depends on the type of diet. In dry cat food, 1200 mg taurine/kg is adequate, but higher concentration (2500 mg taurine/kg dry matter) is required for canned foods because the heating during canning produces products that increase enterohepatic taurine loss or decrease taurine absorption.

Question 72

Diets containing ..... bran or whole ..... may also increase fecal bile acid excretion or alter the enteric bacterial population and lead to increased taurine degradation, and they have been associated with reduced plasma and whole blood taurine concentrations in normal cats.

Answer 72

Diets containing rice bran or whole rice may also increase fecal bile acid excretion or alter the enteric bacterial population and lead to increased taurine degradation, and they have been associated with reduced plasma and whole blood taurine concentrations in normal cats.

Question 73

The highest concentration of free taurine in the body is found within the ............. and ..........., with concentrations 100 to 400 times plasma taurine concentration. Myocardial uptake of taurine is regulated through c........-mediated function of the ...........-adrenergic receptors. Taurine has diverse functions, the most important including modulation of ................... (possibly through myocardial calcium homeostasis), metabolic and osmotic regulation of the ....................., membrane stabilization of photoreceptor cells of the retina, and neuroinhibitor actions in the central nervous system.

Answer 73

The highest concentration of free taurine in the body is found within the myocardium and retina, with concentrations 100 to 400 times plasma taurine concentration. Myocardial uptake of taurine is regulated through cAMP-mediated function of the beta-adrenergic receptors. Taurine has diverse functions, the most important including modulation of contractility (possibly through myocardial calcium homeostasis), metabolic and osmotic regulation of the myocardium, membrane stabilization of photoreceptor cells of the retina, and neuroinhibitor actions in the central nervous system.

Question 74

Taurine Deficiency–Induced Diseases Cats fed taurine-deficient diets for several months may lead to .......?

Answer 74

Central retinal degeneration, reproductive abnormalities in the female, abortion and fetal resorption, stunted kittens with low birth weight and survival, compromised immune function, DCM Not all cats fed a taurine-deficient diets develop DCM, with a range of 20% to 65% of cats developing echocardiographic evidence of DCM. The most significant deteriorations in systolic function (assessed by end-systolic diameter and fractional shortening) occur in the first 4 months of being fed a taurine-deficient diet.[97] Nearly half of cats with taurine deficiency–induced DCM also have evidence of central retinal degeneration on retinal examination.

Question 75

Assessment of Taurine Status Because taurine is highly concentrated within cardiomyocytes, ideal assessment of taurine levels would be measurement of intracellular myocardial taurine content, which has been shown to be markedly decreased in cats with taurine deficiency–induced DCM.[98] Because this is clinically impractical, diagnosis of taurine deficiency is made by measurement of plasma and whole blood taurine concentration. Taurine is concentrated in the ........... and ......................, making whole blood taurine concentration four to fivefold higher than plasma taurine concentration. Plasma taurine concentration is subject to significant fluctuations depending on the fasted state of the cat. In cats fed diets adequate in taurine, plasma taurine concentration was critically low (

Answer 75

Assessment of Taurine Status Because taurine is highly concentrated within cardiomyocytes, ideal assessment of taurine levels would be measurement of intracellular myocardial taurine content, which has been shown to be markedly decreased in cats with taurine deficiency–induced DCM.[98] Because this is clinically impractical, diagnosis of taurine deficiency is made by measurement of plasma and whole blood taurine concentration. Taurine is concentrated in the platelets and granulocytes, making whole blood taurine concentration four to fivefold higher than plasma taurine concentration. Plasma taurine concentration is subject to significant fluctuations depending on the fasted state of the cat. In cats fed diets adequate in taurine, plasma taurine concentration was critically low (

Question 76

Treatment of Taurine Deficiency–Induced Myocardial Failure Treatment of cats with taurine deficiency–induced myocardial failure with taurine (250 mg PO bid) improves and often normalizes systolic function within several weeks to months of supplementation. Initial treatment with positive inotropes including an inodilator (pimobendan) and digoxin, as well as heart failure treatment with furosemide and an ACE inhibitor, is necessary for several months until the beneficial effects of taurine occur. Clinical signs typically improve within 2 weeks, and by 3 to 6 weeks, there is echocardiographic evidence of decreased end-systolic LV diameter, increased fractional shortening, and decreased end-diastolic diameter. Improvements in end-systolic diameter and fractional shortening continue for up to a year after supplementation.[100] Early cardiovascular death within the first month occurs in approximately 38% of treated cats.[100] However, if a cat survives after the first 2 weeks of therapy, there is a 96% chance of long-term survival with complete recovery. Cats with improvement in systolic function can be weaned off all medications as long as their diet has been changed to one with adequate taurine levels. Survival is markedly improved in cats with taurine deficiency–induced cardiomyopathy treated with taurine compared with historical cats with DCM prior to the discovery of this clinical entity (58% vs. 13% 1-year survival).

Answer 76

Treatment of Taurine Deficiency–Induced Myocardial Failure Treatment of cats with taurine deficiency–induced myocardial failure with taurine (250 mg PO bid) improves and often normalizes systolic function within several weeks to months of supplementation. Initial treatment with positive inotropes including an inodilator (pimobendan) and digoxin, as well as heart failure treatment with furosemide and an ACE inhibitor, is necessary for several months until the beneficial effects of taurine occur. Clinical signs typically improve within 2 weeks, and by 3 to 6 weeks, there is echocardiographic evidence of decreased end-systolic LV diameter, increased fractional shortening, and decreased end-diastolic diameter. Improvements in end-systolic diameter and fractional shortening continue for up to a year after supplementation.[100] Early cardiovascular death within the first month occurs in approximately 38% of treated cats.[100] However, if a cat survives after the first 2 weeks of therapy, there is a 96% chance of long-term survival with complete recovery. Cats with improvement in systolic function can be weaned off all medications as long as their diet has been changed to one with adequate taurine levels. Survival is markedly improved in cats with taurine deficiency–induced cardiomyopathy treated with taurine compared with historical cats with DCM prior to the discovery of this clinical entity (58% vs. 13% 1-year survival).

Question 77

RESTRICTIVE CARDIOMYOPATHY RCM is a primary abnormality of diastolic dysfunction characterized by increased ventricular .............and increased diastolic..................., leading to........................... RCM is not a specific disease entity but is a functional term that encompasses a spectrum of pathologic phenotypes and pathophysiology.[101] Idiopathic RCM in people is caused by patchy to diffuse endoperimysial fibrosis and myocyte disarray, with or without some degree of hypertrophy. Abnormalities often involve both the left and right ventricles and lead to left and right heart failure. A separate entity is endomyocardial fibrosis (EMF), which causes the same pathophysiologic abnormality of increased ventricular stiffness. EMF is associated with massive .....................fibrosis involving the endocardium and endomyocardium (Figures 252-6 and 252-7). Unlike some people, cats do not appear to develop EMF secondary to eosinophilic infiltration.[102] The etiology of EMF in cats is unknown, with possible hypotheses including ............-induced or .....................-mediated–induced severe endomyocardial injury followed by ........................... fibrosis.

Answer 77

RESTRICTIVE CARDIOMYOPATHY RCM is a primary abnormality of diastolic dysfunction characterized by increased ventricular stiffness and increased diastolic filling pressures, leading to left atrial or biatrial dilation. RCM is not a specific disease entity but is a functional term that encompasses a spectrum of pathologic phenotypes and pathophysiology.[101] Idiopathic RCM in people is caused by patchy to diffuse endoperimysial fibrosis and myocyte disarray, with or without some degree of hypertrophy. Abnormalities often involve both the left and right ventricles and lead to left and right heart failure. A separate entity is endomyocardial fibrosis (EMF), which causes the same pathophysiologic abnormality of increased ventricular stiffness. EMF is associated with massive replacement fibrosis involving the endocardium and endomyocardium (Figures 252-6 and 252-7). Unlike some people, cats do not appear to develop EMF secondary to eosinophilic infiltration.[102] The etiology of EMF in cats is unknown, with possible hypotheses including viral-induced or immune-mediated–induced severe endomyocardial injury followed by reparative fibrosis.

Question 78

Figure 252-6 Gross pathology of a cat with endomyocardial fibrosis form of restrictive cardiomyopathy. There is a large fibrotic bridging band (arrow) that tethers the papillary muscles and left ventricular free wall to the basilar interventricular septum. There is diffuse, severe endomyocardal fibrosis evident as thickened, white appearance of the endomyocardium with a dense hyperechoic scar. There is severe left atrial dilation, secondary to a noncompliant left ventricle (LV) and markedly elevated left ventricular filling pressure. Ao, Aorta; LA, left atrium.

Answer 78

Figure 252-6 Gross pathology of a cat with endomyocardial fibrosis form of restrictive cardiomyopathy. There is a large fibrotic bridging band (arrow) that tethers the papillary muscles and left ventricular free wall to the basilar interventricular septum. There is diffuse, severe endomyocardal fibrosis evident as thickened, white appearance of the endomyocardium with a dense hyperechoic scar. There is severe left atrial dilation, secondary to a noncompliant left ventricle (LV) and markedly elevated left ventricular filling pressure. Ao, Aorta; LA, left atrium.

Question 79

Figure 252-7 Echocardiogram of the left ventricle of a cat with severe endomyocardial fibrosis and restrictive cardiomyopathy. This two-dimensional echocardiogram of the left ventricle at the level of the papillary muscles shows a large fibrotic bridging band (arrow) tethering the anterior left ventricular free wall to the interventricular septum. There is papillary hypertrophy and mild focal septal hypertrophy at the site of the fibrotic band attachment. LV, Left ventricle.

Answer 79

Figure 252-7 Echocardiogram of the left ventricle of a cat with severe endomyocardial fibrosis and restrictive cardiomyopathy. This two-dimensional echocardiogram of the left ventricle at the level of the papillary muscles shows a large fibrotic bridging band (arrow) tethering the anterior left ventricular free wall to the interventricular septum. There is papillary hypertrophy and mild focal septal hypertrophy at the site of the fibrotic band attachment. LV, Left ventricle.

Question 80

Some people develop RCM as a familial heritable defect, and in a recent report approximately one third of cases were familial and caused by mutations in cardiac troponin I, cardiac troponin T, and α-cardiac actin genes.[105] Another study found that six of nine cases of “idiopathic” RCM were actually caused by mutations in cardiac troponin I.[106] Familial RCM is a collection of heterogenous disorders with a spectrum of cardiac phenotypes, including HCM or DCM in family members. Histopathologic abnormalities in idiopathic RCM often resemble HCM, because more than 40% of cases have myocyte ............., interstitial ............, and ............... identical to histopathologic abnormalities seen in HCM.[105] Although RCM, HCM, and DCM have distinct clinical differences, the causative mutations in familial cases often involve the same ....................... mutations. Comparing in vitro effects of cardiac troponin .... mutations in RCM and HCM, the mutations causing RCM lead to greater calcium sensitivity and more severe diastolic impairment than the mutations causing familial HCM, likely leading to the restrictive phenotype.[107],[108] It is likely that variations in the location of the mutation within the specific functional domain of the sarcomeric genes can result in different clinical phenotypes of dilated, restrictive, or hypertrophic cardiomyopathy.

Answer 80

Some people develop RCM as a familial heritable defect, and in a recent report approximately one third of cases were familial and caused by mutations in cardiac troponin I, cardiac troponin T, and α-cardiac actin genes.[105] Another study found that six of nine cases of “idiopathic” RCM were actually caused by mutations in cardiac troponin I.[106] Familial RCM is a collection of heterogenous disorders with a spectrum of cardiac phenotypes, including HCM or DCM in family members. Histopathologic abnormalities in idiopathic RCM often resemble HCM, because more than 40% of cases have myocyte disarray, interstitial fibrosis, and hypertrophy identical to histopathologic abnormalities seen in HCM.[105] Although RCM, HCM, and DCM have distinct clinical differences, the causative mutations in familial cases often involve the same sarcomeric mutations. Comparing in vitro effects of cardiac troponin T mutations in RCM and HCM, the mutations causing RCM lead to greater calcium sensitivity and more severe diastolic impairment than the mutations causing familial HCM, likely leading to the restrictive phenotype.[107],[108] It is likely that variations in the location of the mutation within the specific functional domain of the sarcomeric genes can result in different clinical phenotypes of dilated, restrictive, or hypertrophic cardiomyopathy.

Question 81

No familial basis of RCM has been reported in cats. There appears to be a female predisposition in cats, as 73% of cats in one report were female.[2] Mean age of diagnosis in a case series of 22 cats was 7.1 ± 3.1 years.[2] Over half (55%) of cats present with clinical signs of dyspnea. Auscultation abnormalities are less common because only 36% of cats had a murmur, 23% of cats had a gallop, and 14% of cats had an arrhythmia evident.[2] Other clinical abnormalities may include poor body condition and ascites.

Answer 81

No familial basis of RCM has been reported in cats. There appears to be a female predisposition in cats, as 73% of cats in one report were female.[2] Mean age of diagnosis in a case series of 22 cats was 7.1 ± 3.1 years.[2] Over half (55%) of cats present with clinical signs of dyspnea. Auscultation abnormalities are less common because only 36% of cats had a murmur, 23% of cats had a gallop, and 14% of cats had an arrhythmia evident.[2] Other clinical abnormalities may include poor body condition and ascites.

Question 82

Thoracic Radiographs Cardiomegaly, including left atrial dilation or biatrial dilation, is seen in a majority of cats with RCM (73%). Pleural effusion is common (in 55% of cats), followed by pulmonary edema (41%) and ascites (23%). Pulmonary venous distension may be seen secondary to left-sided heart failure. A dilated caudal vena cava may be seen secondary to right heart failure.

Answer 82

Thoracic Radiographs Cardiomegaly, including left atrial dilation or biatrial dilation, is seen in a majority of cats with RCM (73%). Pleural effusion is common (in 55% of cats), followed by pulmonary edema (41%) and ascites (23%). Pulmonary venous distension may be seen secondary to left-sided heart failure. A dilated caudal vena cava may be seen secondary to right heart failure.

Question 83

Electrocardiogram The ECG is insensitive for detection of cardiac chamber enlargement but is the test of choice for evaluation of cardiac arrhythmias. Arrhythmias are invariably present in cats with RCM, with the most common arrhythmias including ventricular premature complexes and supraventricular tachycardia. Other arrhythmias may include atrial premature complexes, atrial fibrillation, ventricular tachycardia, atrial standstill, third-degree atrioventricular block, and bundle branch blocks (left or right).

Answer 83

Electrocardiogram The ECG is insensitive for detection of cardiac chamber enlargement but is the test of choice for evaluation of cardiac arrhythmias. Arrhythmias are invariably present in cats with RCM, with the most common arrhythmias including ventricular premature complexes and supraventricular tachycardia. Other arrhythmias may include atrial premature complexes, atrial fibrillation, ventricular tachycardia, atrial standstill, third-degree atrioventricular block, and bundle branch blocks (left or right).

Question 84

Echocardiography The classic echocardiographic abnormalities of RCM include significant left atrial dilation (LA : Ao >1.8) or biatrial dilation in the face of a normal or near normal LV (Figure 252-8). The LV end-diastolic wall thickness is normal to near normal (

Answer 84

Echocardiography The classic echocardiographic abnormalities of RCM include significant left atrial dilation (LA : Ao >1.8) or biatrial dilation in the face of a normal or near normal LV (Figure 252-8). The LV end-diastolic wall thickness is normal to near normal (

Question 85

Figure 252-8 Echocardiogram of a cat with severe unclassified cardiomyopathy. A, Color flow Doppler of the atrioventricular valves shows mild centrally arising mitral and tricuspid regurgitation, as well as severe left atrial (LA) and right atrial (RA) dilation. The left ventricular wall thickness, size, and function were normal. B, This two-dimensional echocardiogram from the right parasternal cross-sectional view at the level of the papillary muscles shows equivocal septal hypertrophy (A, interventricular septal thickness at diastole of 5.9 mm), normal left ventricular end-diastolic diameter (B, 15.2 mm), and normal left ventricular free wall diastolic thickness (C, 4.1 mm). There was normal systolic myocardial function. LV, Left ventricle; RV, right ventricle.

Answer 85

Figure 252-8 Echocardiogram of a cat with severe unclassified cardiomyopathy. A, Color flow Doppler of the atrioventricular valves shows mild centrally arising mitral and tricuspid regurgitation, as well as severe left atrial (LA) and right atrial (RA) dilation. The left ventricular wall thickness, size, and function were normal. B, This two-dimensional echocardiogram from the right parasternal cross-sectional view at the level of the papillary muscles shows equivocal septal hypertrophy (A, interventricular septal thickness at diastole of 5.9 mm), normal left ventricular end-diastolic diameter (B, 15.2 mm), and normal left ventricular free wall diastolic thickness (C, 4.1 mm). There was normal systolic myocardial function. LV, Left ventricle; RV, right ventricle.

Question 86

In cases of EMF, the endomyocardium appears thickened with a dense hyperechoic scar that is sharply delineated from the normal underlying myocardium. The pathognomic feature of EMF is a large fibrotic bridging band that tethers the papillary muscles or LV free wall to the interventricular septum (see Figure 252-7).

Answer 86

In cases of EMF, the endomyocardium appears thickened with a dense hyperechoic scar that is sharply delineated from the normal underlying myocardium. The pathognomic feature of EMF is a large fibrotic bridging band that tethers the papillary muscles or LV free wall to the interventricular septum (see Figure 252-7).

Question 87

There may be .......... and ............... impedance to flow associated with the fibrotic bands causing turbulent blood flow and intraventricular pressure gradients on Doppler interrogation. Like people with EMF, cats may have apical obliteration from dense fibrotic scar, which may decrease LV chamber size. There may be mild to moderate atrioventricular valvular insufficiency because the papillary muscles may become distorted from the scar or the chordae tendinea/valve leaflet may become tethered. There may be focal regions of mild ..................... hypertrophy of the left ventricle.

Answer 87

There may be diastolic and systolic impedance to flow associated with the fibrotic bands causing turbulent blood flow and intraventricular pressure gradients on Doppler interrogation. Like people with EMF, cats may have apical obliteration from dense fibrotic scar, which may decrease LV chamber size. There may be mild to moderate atrioventricular valvular insufficiency because the papillary muscles may become distorted from the scar or the chordae tendinea/valve leaflet may become tethered. There may be focal regions of mild concentric hypertrophy of the left ventricle.

Question 88

One of the defining criteria for diagnosis of RCM is evidence of a restrictive filling pattern seen on PW Doppler interrogation of the mitral inflow. A restrictive filling pattern occurs when there is severe diastolic impairment leading to markedly elevated left atrial pressure and a high left atrial–to-LV diastolic pressure gradient. It is characterized by an increased early diastolic filling velocity (>1 m/s), a decreased atrial filling velocity (2), shortened deceleration time (normal is 59 ± 14 ms), and decreased IVRT (normal is 55 ± 13 ms).[109] Not all cats with EMF have a restrictive filling pattern, and some may have delayed relaxation pattern or a pseudonormal pattern.

Answer 88

One of the defining criteria for diagnosis of RCM is evidence of a restrictive filling pattern seen on PW Doppler interrogation of the mitral inflow. A restrictive filling pattern occurs when there is severe diastolic impairment leading to markedly elevated left atrial pressure and a high left atrial–to-LV diastolic pressure gradient. It is characterized by an increased early diastolic filling velocity (>1 m/s), a decreased atrial filling velocity (2), shortened deceleration time (normal is 59 ± 14 ms), and decreased IVRT (normal is 55 ± 13 ms).[109] Not all cats with EMF have a restrictive filling pattern, and some may have delayed relaxation pattern or a pseudonormal pattern.

Question 89

TDI may be a useful tool to identify diastolic dysfunction in cats with RCM. In people, RCM clinically closely resembles constrictive pericarditis, and TDI is a useful test to differentiate the diseases. Patients with RCM have reduced early diastolic mitral annulus velocity indicative of diastolic dysfunction compared to patients with constrictive pericarditis, with a sensitivity of 89% in one study.[110] Only one study has evaluated cats with unclassified/restrictive cardiomyopathy by PW TDI.[38] The cats were classified as UCM rather than RCM but had the same echocardiographic abnormalities of left atrial or biatrial dilation with no concentric hypertrophy or systolic dysfunction. Six of nine cats with UCM had reduced peak diastolic velocity of the mitral annulus and LV free wall. These six cats also had reduced isovolumetric relaxation time and decreased rate of maximal diastolic acceleration and deceleration.[38]

Answer 89

TDI may be a useful tool to identify diastolic dysfunction in cats with RCM. In people, RCM clinically closely resembles constrictive pericarditis, and TDI is a useful test to differentiate the diseases. Patients with RCM have reduced early diastolic mitral annulus velocity indicative of diastolic dysfunction compared to patients with constrictive pericarditis, with a sensitivity of 89% in one study.[110] Only one study has evaluated cats with unclassified/restrictive cardiomyopathy by PW TDI.[38] The cats were classified as UCM rather than RCM but had the same echocardiographic abnormalities of left atrial or biatrial dilation with no concentric hypertrophy or systolic dysfunction. Six of nine cats with UCM had reduced peak diastolic velocity of the mitral annulus and LV free wall. These six cats also had reduced isovolumetric relaxation time and decreased rate of maximal diastolic acceleration and deceleration.[38]

Question 90

TREATMENT Most cats diagnosed with RCM have clinical evidence of CHF and should be treated with furosemide and an ACE inhibitor. Because ATE is very common in cats with RCM (45% incidence in one study), cats with significant atrial dilation should be placed on prophylactic anticoagulant therapy.[111] Because tachycardia greatly increases .......... filling pressure in the presence of severe ............ dysfunction, antiarrhythmic control of tachyarrhythmias is paramount. The choice of antiarrhythmics is unlimited given the normal systolic myocardial function. Supraventricular tachyarrhythmias (i.e., atrial fibrillation or supraventricular tachycardia) may be treated with atenolol or diltiazem, with the addition of digoxin if there is still inadequate rate control. Ventricular arrhythmias may be treated with atenolol or sotalol, and mexiletine may be added for additional synergistic antiarrhythmic control of refractory ventricular arrhythmias.

Answer 90

TREATMENT Most cats diagnosed with RCM have clinical evidence of CHF and should be treated with furosemide and an ACE inhibitor. Because ATE is very common in cats with RCM (45% incidence in one study), cats with significant atrial dilation should be placed on prophylactic anticoagulant therapy.[111] Because tachycardia greatly increases diastolic filling pressure in the presence of severe diastolic dysfunction, antiarrhythmic control of tachyarrhythmias is paramount. The choice of antiarrhythmics is unlimited given the normal systolic myocardial function. Supraventricular tachyarrhythmias (i.e., atrial fibrillation or supraventricular tachycardia) may be treated with atenolol or diltiazem, with the addition of digoxin if there is still inadequate rate control. Ventricular arrhythmias may be treated with atenolol or sotalol, and mexiletine may be added for additional synergistic antiarrhythmic control of refractory ventricular arrhythmias.

Question 91

PROGNOSIS Prognosis for cats with RCM is poor, with a median survival time of 132 days in one study of 22 cats with RCM.[2] Identification of restrictive filling pattern in people with heart failure confers a poorer prognosis, independent of the underlying heart disease present. People with heart failure and a restrictive filling pattern identified on PW Doppler interrogation of mitral inflow had a fourfold increase in mortality compared with heart failure patients without restrictive filling pattern.[112]

Answer 91

PROGNOSIS Prognosis for cats with RCM is poor, with a median survival time of 132 days in one study of 22 cats with RCM.[2] Identification of restrictive filling pattern in people with heart failure confers a poorer prognosis, independent of the underlying heart disease present. People with heart failure and a restrictive filling pattern identified on PW Doppler interrogation of mitral inflow had a fourfold increase in mortality compared with heart failure patients without restrictive filling pattern.[112]

Question 92

UNCLASSIFIED CARDIOMYOPATHY UCM is a nebulous category including cats with significant left atrial or biatrial dilation despite normal to near normal systolic function, and normal to near-normal LV wall thickness, in the absence of severe atrioventricular valvular dilation. This description is very similar to RCM, and many consider combining categories to UCM-RCM unless there is obvious EMF because it is very difficult to distinguish UCM from myocardial-type RCM. A .................. filling pattern on mitral inflow is a characteristic of RCM, but identification of this pattern requires separate...............waves. Often there is EA summation when heart rate is over 150 beats/min, so identification of a restrictive filling pattern may be impossible. Therefore, many clinicians use the term UCM to include cats with atrial or biatrial enlargement with normal LV size and function.

Answer 92

UNCLASSIFIED CARDIOMYOPATHY UCM is a nebulous category including cats with significant left atrial or biatrial dilation despite normal to near normal systolic function, and normal to near-normal LV wall thickness, in the absence of severe atrioventricular valvular dilation. This description is very similar to RCM, and many consider combining categories to UCM-RCM unless there is obvious EMF because it is very difficult to distinguish UCM from myocardial-type RCM. A restrictive filling pattern on mitral inflow is a characteristic of RCM, but identification of this pattern requires separate E and A waves. Often there is EA summation when heart rate is over 150 beats/min, so identification of a restrictive filling pattern may be impossible. Therefore, many clinicians use the term UCM to include cats with atrial or biatrial enlargement with normal LV size and function. Etiology of UCM is unknown.

Question 93

Diastolic dysfunction may be a cause of the atrial dilation. Other causes may include atrial ............. or atrial ................... There is no breed predisposition for UCM, and mean age in a case series of 11 cats was 8.8 ± 4.8 years. Many cats present with clinical signs of dyspnea (64%), tachypnea, and nonspecific signs of lethargy (27%), anorexia, or weight loss. A murmur was auscultated in only half of cats in a case series, and an arrhythmia was uncommon (18%).

Answer 93

Diastolic dysfunction may be a cause of the atrial dilation. Other causes may include atrial myopathy or atrial dysfunction. There is no breed predisposition for UCM, and mean age in a case series of 11 cats was 8.8 ± 4.8 years. Many cats present with clinical signs of dyspnea (64%), tachypnea, and nonspecific signs of lethargy (27%), anorexia, or weight loss. A murmur was auscultated in only half of cats in a case series, and an arrhythmia was uncommon (18%).

Question 94

DIAGNOSTIC TESTING Thoracic radiographs should be obtained because CHF may be present. In a small case series of 11 cats, half had pleural effusion on radiographs, and fewer (9%) had pulmonary edema.[2] Cardiomegaly is commonly seen, as well as left atrial dilation or biatrial dilation. Electrocardiography may reveal an arrhythmia, including ventricular premature complexes (50% of cats) or supraventricular tachycardia (50% of cats).[2] Of interest, 18% of cats in a case series had atrial standstill, which is a rare arrhythmia in cats.[2] It is possible that some cats with UCM have an atrial myopathy, which could lead to infiltrative disease of the sinus node and atrial myocardium, atrial dilation, and atrial standstill. Echocardiography reveals left atrial dilation or biatrial dilation in the face of a relatively normal LV with normal to near-normal wall thickness (

Answer 94

DIAGNOSTIC TESTING Thoracic radiographs should be obtained because CHF may be present. In a small case series of 11 cats, half had pleural effusion on radiographs, and fewer (9%) had pulmonary edema.[2] Cardiomegaly is commonly seen, as well as left atrial dilation or biatrial dilation. Electrocardiography may reveal an arrhythmia, including ventricular premature complexes (50% of cats) or supraventricular tachycardia (50% of cats).[2] Of interest, 18% of cats in a case series had atrial standstill, which is a rare arrhythmia in cats.[2] It is possible that some cats with UCM have an atrial myopathy, which could lead to infiltrative disease of the sinus node and atrial myocardium, atrial dilation, and atrial standstill. Echocardiography reveals left atrial dilation or biatrial dilation in the face of a relatively normal LV with normal to near-normal wall thickness (

Question 95

TREATMENT There is no specific therapy for UCM, but therapy is necessary for heart failure, possibly prophylactic anticoagulant therapy, and antiarrhythmic therapy for significant arrhythmias. Treatment is the same as outlined in the RCM section. Prognosis for cats with UCM is variable. In one study, median survival time in 11 cats with UCM was 925 days. If heart failure is present, prognosis is much poorer, and most cats may survive months to a year.

Answer 95

TREATMENT There is no specific therapy for UCM, but therapy is necessary for heart failure, possibly prophylactic anticoagulant therapy, and antiarrhythmic therapy for significant arrhythmias. Treatment is the same as outlined in the RCM section. Prognosis for cats with UCM is variable. In one study, median survival time in 11 cats with UCM was 925 days. If heart failure is present, prognosis is much poorer, and most cats may survive months to a year.

Question 96

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY ARVC is a rare myocardial disease in cats (diagnosed in 2 of 287 cats with cardiomyopathy) and is more commonly seen in people and Boxer dogs.1 ARVC is characterized by .......... or ................. replacement of .................. in .....................the, sometimes extending in a milder degree to the ......... myocardium.

Answer 96

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY ARVC is a rare myocardial disease in cats (diagnosed in 2 of 287 cats with cardiomyopathy) and is more commonly seen in people and Boxer dogs.1 ARVC is characterized by fatty or fibrofatty replacement of cardiomyocytes in the right ventricle and right atrium, sometimes extending in a milder degree to the LV myocardium.

Question 97

ARVC is familial in people and is a dominant heritable condition in Boxer dogs.[113] Most human familial cases are caused by mutations in various components of the ...............(necessary for cell-to-cell adhesion) including plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2.[114] Mutations in the ryanodine receptor (i.e., the calcium release channel of the sarcoplasmic reticulum) lead to a subtype of ARVD in people with severe polymorphic ventricular tachycardia. A mutation in transforming growth factor beta-3 was found to be associated with an isolated human case of ARVC, with speculations of increased fibrogenesis as a pathophysiologic mechanism of disease.

Answer 97

ARVC is familial in people and is a dominant heritable condition in Boxer dogs.[113] Most human familial cases are caused by mutations in various components of the desmosome (necessary for cell-to-cell adhesion) including plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2.[114] Mutations in the ryanodine receptor (i.e., the calcium release channel of the sarcoplasmic reticulum) lead to a subtype of ARVD in people with severe polymorphic ventricular tachycardia. A mutation in transforming growth factor beta-3 was found to be associated with an isolated human case of ARVC, with speculations of increased fibrogenesis as a pathophysiologic mechanism of disease.

Question 98

The causative mutation of ARVC of Boxer dogs has recently been discovered and involves a ............... protein named ................, which colocalizes with plakophyllin. This mutation greatly decreases the number of ...................., which may lead to loss of mechanical coupling and predispose to .......................... Little is known about the cause of ARVC in cats, and there is only one case series of 12 cats diagnosed with ARVC in the medical literature.[116] Pathophysiologic sequelae of ARVC include severe ........................(3)

Answer 98

The causative mutation of ARVC of Boxer dogs has recently been discovered and involves a desmosomal protein named striatin, which colocalizes with plakophyllin. This mutation greatly decreases the number of gap junctions, which may lead to loss of mechanical coupling and predispose to arrhythmias. Little is known about the cause of ARVC in cats, and there is only one case series of 12 cats diagnosed with ARVC in the medical literature.[116] Pathophysiologic sequelae of ARVC include severe right ventricular myocardial failure, life-threatening ventricular arrhythmias, and sudden death.

Question 99

SIGNALMENT AND CLINICAL ABNORMALITIES There is no breed or sex predilection for ARVC in cats, and mean age of diagnosis was 7.3 ± 5.2 years in one case series of 11 cats diagnosed with ARVC.[116] A majority of cats presented with clinical evidence of right-sided heart failure (67%), including tachypnea, jugular vein distension, ascites, and hepatomegaly. Most cats (67%) have soft right parasternal pansystolic murmurs consistent with tricuspid regurgitation. Syncope was an uncommon presenting complaint in 1 of 11 cats. Other nonspecific signs included lethargy and anorexia in 4 of 11 cats.

Answer 99

SIGNALMENT AND CLINICAL ABNORMALITIES There is no breed or sex predilection for ARVC in cats, and mean age of diagnosis was 7.3 ± 5.2 years in one case series of 11 cats diagnosed with ARVC.[116] A majority of cats presented with clinical evidence of right-sided heart failure (67%), including tachypnea, jugular vein distension, ascites, and hepatomegaly. Most cats (67%) have soft right parasternal pansystolic murmurs consistent with tricuspid regurgitation. Syncope was an uncommon presenting complaint in 1 of 11 cats. Other nonspecific signs included lethargy and anorexia in 4 of 11 cats.

Question 100

Thoracic Radiographs Marked right-sided cardiomegaly is found in all cats diagnosed with ARVC (Web Figure 252-5). Pleural effusion is the most common manifestation of right-sided CHF (in 67% of cats) followed by ascites (in 33% of cats) and dilated caudal vena cava (in 17% of cats).

Answer 100

Thoracic Radiographs Marked right-sided cardiomegaly is found in all cats diagnosed with ARVC (Web Figure 252-5). Pleural effusion is the most common manifestation of right-sided CHF (in 67% of cats) followed by ascites (in 33% of cats) and dilated caudal vena cava (in 17% of cats).

Question 101

Electrocardiogram Ventricular arrhythmias are common in cats with ARVC and may lead to syncope or sudden death (Web Figure 252-6). Arrhythmogenesis is caused by macroreentrant circuits that develop in regions of fibrofatty replacement of cardiomyocytes.[117] Most (75%) of cats in a case series had ventricular premature beats and 38% had ventricular tachycardia.[116] Half of cats were diagnosed with atrial fibrillation, which is secondary to severe right atrial dilation and fibrofatty replacement of cardiomyocytes. Many cats have................ bundle branch block, likely due to the destruction of the right bundle branch from the pathologic process in the right ventricle.

Answer 101

Electrocardiogram Ventricular arrhythmias are common in cats with ARVC and may lead to syncope or sudden death (Web Figure 252-6). Arrhythmogenesis is caused by macroreentrant circuits that develop in regions of fibrofatty replacement of cardiomyocytes.[117] Most (75%) of cats in a case series had ventricular premature beats and 38% had ventricular tachycardia.[116] Half of cats were diagnosed with atrial fibrillation, which is secondary to severe right atrial dilation and fibrofatty replacement of cardiomyocytes. Many cats have right bundle branch block, likely due to the destruction of the right bundle branch from the pathologic process in the right ventricle.

Question 102

Echocardiography Marked right ventricular eccentric hypertrophy (i.e., increased end-diastolic diameter) and right atrial dilation are the classic readily recognized echocardiographic abnormalities in ARVC (Figure 252-9 and Web Figure 252-7; see Table 252-1). There may be right ventricular aneurysms and abnormal muscular trabeculation in the right ventricular apex. Increased right ventricular diastolic pressure leads to diastolic interventricular septal bowing and flattening (paradoxical septal motion).

Answer 102

Echocardiography Marked right ventricular eccentric hypertrophy (i.e., increased end-diastolic diameter) and right atrial dilation are the classic readily recognized echocardiographic abnormalities in ARVC (Figure 252-9 and Web Figure 252-7; see Table 252-1). There may be right ventricular aneurysms and abnormal muscular trabeculation in the right ventricular apex. Increased right ventricular diastolic pressure leads to diastolic interventricular septal bowing and flattening (paradoxical septal motion).

Question 103

The main differential for ARVC in cats is tricuspid valve dysplasia, which causes severe volume overload to the right ventricle and right atrium. Color flow Doppler interrogation of the tricuspid valve in ARVC often reveals mild centrally arising tricuspid regurgitation secondary to annular dilation. The tricuspid valve appears structurally normal, compared with a cat with tricuspid valve dysplasia that would have significant tricuspid regurgitation and a structurally abnormal tricuspid valve with clubbed thickened leaflets and short, thickened, tethered chordae tendineae and abnormal papillary muscles. The distinction is important because prognosis for ARVC is grave compared with tricuspid valve dysplasia. There may be left atrial dilation in some cats with ARVC because end-stage disease may also affect the LV and left atrium

Answer 103

The main differential for ARVC in cats is tricuspid valve dysplasia, which causes severe volume overload to the right ventricle and right atrium. Color flow Doppler interrogation of the tricuspid valve in ARVC often reveals mild centrally arising tricuspid regurgitation secondary to annular dilation. The tricuspid valve appears structurally normal, compared with a cat with tricuspid valve dysplasia that would have significant tricuspid regurgitation and a structurally abnormal tricuspid valve with clubbed thickened leaflets and short, thickened, tethered chordae tendineae and abnormal papillary muscles. The distinction is important because prognosis for ARVC is grave compared with tricuspid valve dysplasia. There may be left atrial dilation in some cats with ARVC because end-stage disease may also affect the LV and left atrium

Question 104

PATHOLOGY Moderate to severe right ventricular dilation and diffuse or segmental wall thinning are the typical gross pathologic abnormalities. Right ventricular aneurysms were present in half of cats in a case series, and there was often transillumination of portions of the right ventricle and right atrium. Hallmark histopatholic lesions were either fibrofatty (75%) or fatty (25%) replacement of cardiomyocytes of the right ventricle. The fibrosis consisted of large patches of replacement-type fibrosis, consistent with reparative process after significant myocardial necrosis. Replacement fibrosis was also present in the left ventricle in a majority of cats (83%). Multifocal myocarditis was common in both ventricles and atria. Cell death may be mediated by apoptosis and programmed cell death because 75% of cats had evidence of apoptotic myocytes in the right ventricle and left ventricle.

Answer 104

PATHOLOGY Moderate to severe right ventricular dilation and diffuse or segmental wall thinning are the typical gross pathologic abnormalities. Right ventricular aneurysms were present in half of cats in a case series, and there was often transillumination of portions of the right ventricle and right atrium. Hallmark histopatholic lesions were either fibrofatty (75%) or fatty (25%) replacement of cardiomyocytes of the right ventricle. The fibrosis consisted of large patches of replacement-type fibrosis, consistent with reparative process after significant myocardial necrosis. Replacement fibrosis was also present in the left ventricle in a majority of cats (83%). Multifocal myocarditis was common in both ventricles and atria. Cell death may be mediated by apoptosis and programmed cell death because 75% of cats had evidence of apoptotic myocytes in the right ventricle and left ventricle.

Question 105

TREATMENT Treatment of cats with ARVC is very similar to treatment of cats with DCM. Positive inotropic therapy is necessary to treat the severe right ventricular myocardial failure, and treatment consists of digoxin and pimobendan. CHF is treated with furosemide and an ACE inhibitor. Anticoagulant therapy is almost always indicated because cats often have profound right atrial dilation and a very high risk of pulmonary thromboembolism. Antiarrhythmic therapy may be necessary for treatment of severe ventricular arrhythmias or supraventricular tachyarrhythmias and is outlined in the DCM section. Prognosis for cats with ARVC is grave. In a case series of 12 cats with ARVC, 75% of cats died or were euthanized due to profound right heart failure or ATE, with a median survival time of 1 month in heart failure cases.[116]

Answer 105

TREATMENT Treatment of cats with ARVC is very similar to treatment of cats with DCM. Positive inotropic therapy is necessary to treat the severe right ventricular myocardial failure, and treatment consists of digoxin and pimobendan. CHF is treated with furosemide and an ACE inhibitor. Anticoagulant therapy is almost always indicated because cats often have profound right atrial dilation and a very high risk of pulmonary thromboembolism. Antiarrhythmic therapy may be necessary for treatment of severe ventricular arrhythmias or supraventricular tachyarrhythmias and is outlined in the DCM section. Prognosis for cats with ARVC is grave. In a case series of 12 cats with ARVC, 75% of cats died or were euthanized due to profound right heart failure or ATE, with a median survival time of 1 month in heart failure cases.[116]