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Companion animal practice

Feline cardiomyopathy

Luca Ferasin

Luca Ferasin graduated from the University of Bologna, Italy, in 1992, and gained a PhD for research in the field of endocrinology from the BBSRC in Cambridge in 1996. Following three years as assistant professor at the University of Padova, Italy, he moved to the University of Bristol and taught feline and canine cardiorespiratory medicine. In 2006 he was appointed associate professor in veterinary cardiology at the University of Minnesota, USA. He returned to the UK in 2008 and is currently a visiting cardiology consultant in southern England and northern Italy. He holds the RCVS certificate in cardiology, the certificate in teaching and learning in higher education, and the European College of Veterinary Internal Medicine diploma in cardiology. He is an RCVS recognised specialist in veterinary cardiology.

Cardiomyopathy is the most common form of heart disease observed in cats and patients present with a wide spectrum of structural and functional cardiac abnormalities. Although several attempts have been made to standardise the classification of the various forms of cardiomyopathy, substantial disagreement still exists among cardiologists since classification criteria are often subjective and are continuously evolving as the aetiology of myocardial disease becomes better understood. This article describes the current classification of cardiomyopathies, as well as the pathophysiology, clinical findings and treatment of the disease in feline patients.

Traditional classification According to the World Health Organization, cardio­ myopathy is defined as a ‘disease of myocardium associated with cardiac dysfunction’ (Richardson and others 1996). Currently, its classification is pri­ marily based on echocardiographic examination (Table 1), although there is a substantial phenotypic variability within the same form of cardiomyopathy (Fig 1) and this often causes subjective interpretations of echocardiographic diagnosis, especially by inexpe­ rienced ultrasonographers. Pathological investigation is an alternative approach, but this is less relevant to practical clinical considerations.

Hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM) represents the most common myocardial disease in cats. It is charac­ terised by increased cardiac mass associated with left ventricular hypertrophy (LVH), which can affect differ­ ent portions of the interventricular septum (IVS) and/ or left ventricular free wall (LVFW). These lesions can

be accompanied by left atrial dilation, aneurismal thin­ ning of the left ventricle (LV) apex, right ventricular hypertrophy and right atrial enlargement. Hypertrophic obstructive cardiomyopathy is a form of HCM that is associated with dynamic outflow obstruction (see systolic anterior motion, p 209).

Restrictive cardiomyopathy Restrictive cardiomyopathy (RCM) is characterised by myocardial stiffness and diastolic dysfunction (restric­ tive pathophysiology), and is the second most common form of cardiomyopathy in cats (approximately 20 per cent of referred feline cardiomyopathy cases [Ferasin and others 2003]). The spectrum of phenotypes in RCM is even wider than that observed in HCM. In the human literature, RCM has both myocardial and endomyocardial forms (Hare 2008), and this classi­ fication has also been used to describe RCM in cats (Fox 2004). The myocardial form of feline RCM is characterised by restrictive filling, a normal or mildly thickened LVFW or IVS, apparently preserved systolic function and severe atrial (often bi-atrial) enlarge­

Table 1: Criteria used for the traditional classification of feline cardiomyopathy

doi:10.1136/inp.e2271 Provenance: Commissioned and peer-reviewed

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Hypertrophic cardiomyopathy

Restrictive cardiomyopathy

Dilated cardiomyopathy

LVH ± RVH. It can present in different forms: concentric, segmental or asymmetric. The left atrium is often enlarged. Dynamic outflow obstruction (ie, systolic anterior motion) may be present

Normal or nearnormal LV thickness. Restrictive physiology with apparently normal systolic function. Severe left atrial (or bi-atrial) enlargement is common

Dilated and hypocontractile LV ± RV chambers. Atrial (or bi-atrial) enlargement

Arrhythmogenic right ventricular cardiomyopathy Dilated and hypocontractile RV with little involvement of the LV. Right atrial enlargement

Modified from Ferasin (2009a) LVH Left ventricular hypertrophy, RVH Right ventricular hypertrophy, LV Left ventricle, RV Right ventricle

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Unclassified cardiomyopathy Myocardial diseases that do not readily fit into any other group

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Companion animal practice

IVS IVS IVS

LVFW LVFW

LVFW

B

A

C

IVS IVS

IVS

LA

LVFW

LA

LVFW LVFW

D

F

E

RVFW

RVFW

IVS

IVS

RVFW IVS LVFW

LVFW

H

G

RVFW IVS

LVFW J

I

LVFW

Fig 1: Echocardiographic B-mode and M-mode images showing the wide spectrum of feline cardiomyopathy. (a) Hypertrophic cardiomyopathy (HCM) with diffuse and substantial concentric left ventricular hypertrophy (LVH). (b) HCM with segmental LVH. (c) HCM with diffuse and substantial asymmetric LVH affecting primarily the interventricular septum (IVS). (d) HCM with diffuse and substantial asymmetric LVH affecting primarily the left ventricular free wall (LVFW). (e) Myocardial form of restrictive cardiomyopathy (RCM). (f) Endomyocardial form of RCM with an extensive fibrotic bridge crossing the left ventricular lumen. (g) Dilated right ventricle and thinning of the right ventricular free wall (RVFW) in arrhythmogenic right ventricular cardiomyopathy. (h) Dilated left ventricle (LV) and thinning of the LVFW in dilated cardiomyopathy. (i,j) Echocardiographic M-mode images of the LV at the level of the papillary muscles showing regional hypocontractility and hyperechogenicity of the LVFW (i) and IVS (j) secondary to myocardial ischaemia. LA Left atrium

ment. The endomyocardial form of feline RCM dif­ fers from the myocardial form due to the presence of extensive reparative fibrotic lesions, which affect pri­ marily the LV and can present as large scars bridging the ventricular lumen.

Dilated cardiomyopathy A severely dilated LV chamber and hypocontractile myocardium represent the main features of dilated cardiomyopathy (DCM). This used to be one of the most common forms of feline cardiac disease until Pion and others (1987) reported the association between taurine deficiency and DCM. This cardiomyopathy is

reversible if oral taurine supplementation is promptly instituted. Based on this discovery, food companies increased taurine concentration in commercial feline diets with a dramatic reduction of the risk of taurine deficiency in the following years. Nevertheless, some rare cases of DCM that occur secondarily to taurine deficiency are still observed, although they are nor­ mally related to a non-conventional diet (ie, vegetar­ ian/vegan diets or canine diets). Conversely, some cases of DCM diagnosed in non-taurine-deficient cats may be a manifestation of an end-stage form of another cardiac disease such as HCM, atrioventricular (AV) valvular dysplasia, ischaemic myocardial disease, In Practice  April 2012 | Volume 34 | 204–213

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Companion animal practice sustained rapid tachycardia (tachycardiomyopathy) or unrecognised episodes of toxicity or viral infection.

ARVC may present with a variety of arrhythmias and conduction disturbances (Harvey and others 2005).

Arrhythmogenic right ventricular cardiomyopathy

Unclassified cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterised by markedly enlarged right chambers with a thin and hypokinetic myocardial free wall, while the left chambers are minimally involved. ARVC is one of the major causes of sudden cardiac death in young people due to the presence of malig­ nant arrhythmias (Hare 2008). Similarly, cats with

A significant number of feline myocardial diseases show features that are not typical of any other commonly recognised cardiomyopathy and are therefore described as ‘unclassified’, although they are likely to be an evolu­ tionary phase of another recognised form of cardiomy­ opathy, (eg, an early or end-stage HCM or myocardial infarction) rather than an individual pathological entity (Cesta and others 2005, Ferasin 2009a) (Box 1).

Box 1: Phenotypic classification: does it really matter? The classic differentiation of cardiomyopathy as hypertrophic, restrictive or dilated mixes structural changes (eg, hypertrophy and dilation) with functional abnormalities (eg, a restrictive pattern of ventricular filling). Consequently, confusion may arise because the same disease could appear in two categories, forcing many clinicians to consider an additional category called ‘unclassified cardiomyopathy’. Although some lesions may appear almost identical on echocardiographic examination, they may originate from different aetiologies (eg, valvular, ischaemic or inflammatory diseases). This is because the structural remodelling

and compensatory mechanisms may be similar, even if they are initiated by different pathologies. Moreover, rhythmic disturbances and enhanced arrhythmogenicity also participate in heart remodelling (tachycardiomyopathy) and should be considered in the current classification of cardiomyopathy. During the natural course of the disease, myocardial lesions may initially affect the left ventricle and subsequently, as a consequence of increased pulmonary arterial pressure (pulmonary hypertension), the right heart chambers can appear as the only affected regions, mimicking an arrhythmogenic right ventricular cardiomyopathy.

RVFW RA IVS

Ao

RVOT

LA

LVFW

LAu

B

A

RVFW

RA

RVOT Ao

IVS LA

LAu

LVFW

C

D

Echocardiographic appearance may vary during the progression of myocardial disease. These echocardiographic images are from a 13-year old female neutered domestic shorthair cat presented initially for sudden-onset dyspnoea. All images are obtained from the right parasternal short-axis view. (a) Diffuse and substantial asymmetric hypertrophy affecting the left ventricular free wall (LVFW) and part of the interventricular septum (IVS). The right ventricle (RV) appears normal. (b) Significant dilation of the left atrium (LA) and left auricle (LAu). The echocardiographic features in (a) and (b) would be consistent with a diagnosis of hypertrophic cardiomyopathy. (c,d) The same patient when presented nine months later for follow-up. The left side of the heart seems ‘normalised’ while the RV and right atrium (RA) appear dilated. There is ‘flattening’ of the IVS secondary to RV pressure/volume overload. These findings could mimic a form of arrhythmogenic right ventricular cardiomyopathy. This case demonstrates how the same myocardial abnormality can present with different phenotypes during the natural course of the disease. RVFW Right ventricular free wall, Ao Aorta, RVOT Right ventricular outflow tract

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Companion animal practice

IVS

LVFW A

Myocardial hypertrophy There is no consensus on criteria to define LVH. Wagner and others (2010) compared different defi­ nitions of LVH (Table 2) and concluded that differ­ ent criteria for LVH yield different diagnoses and that there is limited agreement between M-mode and B-mode measurements. Furthermore, false positive results may be generated by M-mode measurements due to the presence of false tendons (Fig 2), which are often difficult to identify with this technique and can be easily and erroneously included in the measurement of the IVS thickness.

Aetiology and epidemiology Different studies report different median ages of cats diagnosed with cardiomyopathy, which may be due to varying feline populations at different veterinary institutions. However, with some exceptions, cats affected by cardiomyopathy are generally mature indi­ viduals, although cardiomyopathy can be recognised in younger animals. Male cats seem to be more affected than females. Some Maine coon, ragdoll, Norwegian forest, Persian and Burmese cats may be genetically predisposed, but the majority of cardiomyopathy cases in practice are in domestic shorthair cats. The primary aetiology of feline cardiomyopathy is not fully understood, although familial HCM has been described in different breeds (eg, Maine coon, ragdoll and British shorthair cats). A causative mutation for HCM has been identified in the sarcomeric gene for the cardiac myosin binding protein C (MYBPC3) both in Maine coons (Meurs and others 2005) and ragdolls (Meurs and others 2007), although this mutation is located in different regions of the same gene in each breed. Not all cats with this mutation go on to develop HCM and, similarly, HCM can be diagnosed in cats that appear negative on genetic testing. It is therefore possible that other mutations play a role in the phenotypical expression of HCM, and not just at a sarcomeric level. Primary HCM needs to be differentiated from sec­ ondary LVH caused by LV pressure overload (ie, LV outflow obstruction, systemic hypertension), hyper­ somatotropism and hyperthyroidism. However, it has been observed that hyperthyroid cats present with only a modest septal hypertrophy (Connolly and others 2005).

Fig 2: (a) M-mode and (b) B-mode echocardiographic images of the left ventricle of a cat showing a false tendon (arrows), which could easily be included in the interventricular septum (IVS) measurement, especially when a suboptimal imaging setting is used. Both images are obtained from the right parasternal shortaxis view. LVFW Left ventricular free wall

IVS

LVFW

B

Other causes of myocardial hypertrophy are given in Table 3.

Pathophysiology Several cardiac functional abnormalities are observed in cats that are affected by cardiomyopathy.

Diastolic dysfunction Feline cardiomyopathy is inevitably accompanied by reduced ventricular relaxation, which can be second­ ary to myocardial hypertrophy, interstitial fibrosis,

Table 2: Different classification criteria to determine left ventricular hypertrophy on echocardiographic examination in cats Method

Definition

Type of echocardiographic assessment

LVH5·5-MM

IVSd or LVFWd 5·5 mm

M-mode, LV in right parasternal short-axis view

LVH6·0-MM

IVSd or LVFWd 6·0 mm

M-mode, LV in right parasternal short-axis view

LVH5·5-BM

IVSd or LVFWd 5·5 mm

B-mode, LV in right parasternal short-axis view

LVH6·0-BM

IVSd or LVFWd 6·0 mm

B-mode, LV in right parasternal short-axis view

LVH50%

>50 per cent of one wall segment or 25 per cent of two neighbouring wall segments 6·0 mm

B-mode, LV in right parasternal short- or long-axis view

Modified from Wagner and others (2010) LVH Left ventricular hypertrophy, IVSd Interventricular septum in diastole, LVFWd Left ventricular free wall in diastole, LV Left ventricle

Table 3: Potential causes of myocardial lesions to consider before making a diagnosis of primary cardiomyopathy Potential cause of myocardial hypertrophy

Potential myocardial lesion observed

Systemic hypertension

Concentric LVH

Left or right outflow obstruction

Concentric LVH or RVH

Acromegaly

Concentric LVH

Myocardial tumours (eg, lymphomas, mesotheliomas)

Concentric symmetric or asymmetric LVH and hypokinesis

Hyperthyroidism

Modest septal hypertrophy

Dystrophin-deficient hypertrophic feline muscular dystrophy

Concentric LVH and hypokinesis, hyperechoic endocardium

Myocardial ischaemia

Depressed and hypokinetic myocardial areas, ventricular chamber dilation

Mitral/tricuspid dysplasia

LV/RV dilation and LA/RA enlargement

Myocarditis

Concentric or asymmetric LVH or RVH

Modified from Ferasin (2009a) LVH Left ventricular hypertrophy, RVH Right ventricular hypertrophy, LV Left ventricle, RV Right ventricle, LA Left atrium, RA Right atrium In Practice  April 2012 | Volume 34 | 204–213

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Companion animal practice

B

A

Fig 3: (a) Eleven-year-old male neutered domestic shorthair cat presented with sudden-onset pain and hindlimb paresis caused by an arterial thromboembolism. (b) The cat’s skin in the metatarsal region is dark blue, which is typical of peripheral cyanosis secondary to peripheral hypoperfusion. (c) Echocardiographic image of spontaneous echocontrast or ‘smoke’ present in the left atrial cavity (arrows), indicating a risk of development of intracavitary thrombi. (d) Intracavitary thrombus lodged in the left auricular appendage (arrows). The cat was diagnosed with a form of restrictive cardiomyopathy complicated by the presence of an intracavitary thrombus. LA Left atrium, LAu Left auricle, RA Right atrium, Ao Aorta, RVOT Right ventricular outflow tract

LAu

RVOT

RA Ao LA LA

LAu C

loss of cellular architecture or a combination of these mechanisms. An increased heart rate may also exac­ erbate the diastolic dysfunction by reducing the time available for ventricular filling and for coronary blood flow, which may lead to myocardial ischaemia. The diastolic dysfunction causes an increase in the LV and left atrium (LA) filling pressure, resulting in pulmo­ nary venous hypertension and eventually pulmonary oedema and/or pleural effusion (congestive heart failure [CHF]).

D

paralysis, renal infarction or sudden death. Although not all patients with echo­cardiographic evidence of intracavitary thrombi develop an arterial thrombo­ embolism (ATE), this finding usually represents a severe risk of haemodynamic complication (Fig 3).

Arrhythmias Unpublished studies by the author based on 24-hour ECG Holter recordings (Fig 4) show that almost all cats affected by cardiomyopathy suffer from significant

Systolic dysfunction Although reduced myocardial contractility is a pre­ dominant feature of DCM and ARVC, systolic dys­ function has also been demonstrated in cats with HCM by pulsed tissue Doppler imaging (TDI) techniques (Koffas and others 2006). Systolic impairment can appear in all forms of cardiomyopathy accompanied by ischaemia and replacement fibrosis, and systolic dysfunction will result in increased ventricular filling pressure and CHF.

Arterial thromboembolism An altered blood flow or blood stasis within the car­ diac chambers can increase the risk of red blood cell aggregation and intracavitary thrombus formation, especially at the level of an abnormally enlarged left auricle. When a thrombus or a fragment of it dislodges and moves into the systemic circulation via the aorta, it can block one of the major arteries causing limb paresis/

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Fig 4: Twenty-four-hour ECG (Holter) monitoring in a cat. This advanced ECG recording technique allows the identification of paroxysmal arrhythmias and intermittent conduction abnormalities in patients affected by cardiomyopathy

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Companion animal practice ventricular or supraventricular arrhythmias. Further­ more, many patients with cardiomyopathy have con­ duction abnormalities with complete AV block being the most common finding. The haemodynamic dis­ turbances secondary to arrhythmias contribute to the complex pathophysiology of feline cardiomyopathy.

Myocardial ischaemia Regional myocardial ischaemia is commonly rec­ ognised in feline patients with all forms of cardio­ myopathy and is often associated with replacement fibrosis (Fox 2003a, 2004, Cesta and others 2005). Ischaemia can be secondary to intramural coronary arterial disease caused by myocardial hypertrophy, and is frequently followed by malignant arrhythmias, as well as systolic and diastolic impairment. The sig­ nificant elevation of cardiac troponin-I (cTn-I) in cats with HCM might indicate ongoing myocardial dam­ age, possibly secondary to a concurrent myo­cardial infarction (Connolly and others 2003).

Systolic anterior motion Systolic anterior motion (SAM) of the mitral valve is a form of dynamic LV outflow obstruction that is present in approximately half of feline HCM cases. It is char­ acterised by an abrupt movement of the anterior leaflet

of the mitral valve towards the IVS, interfering with the LV outflow in mid-systole. The abnormal position of the mitral leaflet in systole is also responsible for a simultaneous mitral regurgitation, resulting in a typi­ cal ‘double jet’ on colour Doppler echocardiography. The abnormal movement of the septal leaflet can also be observed on M-mode imaging of the mitral valve and on spectral Doppler evaluation of the LV outflow tract, with an increased aortic peak flow velocity and an abrupt acceleration in mid-systole, which produces a characteristic asymmetric waveform (Fig 5). The dynamic obstruction caused by SAM has many consequences: ■■ It reduces the stroke volume, hence the cardiac output; ■■ It causes LV pressure overload, which may stimu­ late further cardiac hypertrophy; ■■ Mitral regurgitation may lead to atrial remodelling (LA dilation); ■■ The continuous mechanical contact between the septal mitral leaflet and the proximal IVS induces fibrotic lesions (‘contact lesions’) that can affect the normal function of both affected anatomical parts. The blood flow turbulence originating during SAM is also responsible for the presence of systolic murmurs on auscultation in many cats with cardiomyopathy.

IVS Ao

LVOT

LA

LVFW

B

A

Fig 5: Systolic anterior motion of the mitral valve (MV) in a six-year-old male neutered domestic shorthair cat. (a) Right parasternal long-axis B-mode echocardiography with colour Doppler interrogation of the MV area and left ventricular outflow tract (LVOT) showing the typical ‘double jet’ during the dynamic outflow obstruction. (b) Spectral Doppler interrogation of the LVOT showing increased aortic outflow velocity and the characteristic asymmetry with a mid-systolic ‘step’ (arrows). (c) Right parasternal short-axis M-mode echocardiography of the left ventricle (LV) at the level of the MV showing a mid-systolic movement of the septal mitral leaflet towards the interventricular septum (IVS) (arrows). (d) Right parasternal long-axis colour M-mode Doppler echocardiography of the LV at the level of the MV showing a mid-systolic jet during the abnormal movement of the mitral septal leaflet (arrows). LVFW Left ventricular free wall, LA Left atrium, Ao Aorta

IVS

IVS

LVFW C

D

LVFW

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Companion animal practice

Box 2: Is SAM secondary to HCM or vice versa? Despite a widespread belief among clinicians, systolic anterior motion (SAM) of the mitral valve is not necessarily associated with myocardial hypertrophy. Although the degree of dynamic obstruction is related to the severity of left ventricular hypertrophy (LVH), it could be speculated that LVH may not solely be a phenotypical manifestation of a primary hypertrophic cardiomyopathy (HCM) but may also be a consequence of the left ventricle (LV) pressure overload caused by the outflow obstruction (Schober and Todd 2010). Furthermore, several cases of feline SAM are observed in the absence of LVH, and this could represent either an early stage of the disease not yet accompanied by LVH, or a degree of LV pressure overload not sufficient to stimulate hypertrophy. Understanding the exact pathophysiology of SAM may provide valuable information for treating cats with obstructive HCM.

The cause of SAM is not fully understood and several hypotheses have been suggested, with altered LV geometry associated with intrinsic mitral valve abnormalities being the most plausible explanation (Ferasin 2009a, Schober and Todd 2010) (Box 2).

Clinical findings The clinical presentation of cats affected by cardiomy­ opathy does not differ between the various forms of the disease, so it is more practical to approach all these cases simply as patients with ‘myocardial disease’.

Heart murmurs Heart murmurs are very common in cats with cardio­ myopathy (approximately 60 per cent of cases [Ferasin 2009a]) and usually originate from dynamic left ven­ tricular outflow tract obstruction and/or mitral regur­ gitation (Fig 6). The murmurs are systolic, often with variable intensity, and can easily be heard over both parasternal regions. They may be present at rest or may become audible when the heart rate and cardiac contrac­ tility increase (eg, during stress or excitement). Several cases of cardiomyopathy are diagnosed in asymptomatic cats following the detection of a heart murmur. Murmurs originating from SAM can also be present in the absence of echocardiographically detectable LVH and, for this reason, may allow early identification of animals that may develop myocardial changes later in life.

Muffled heart sounds Muffled heart sounds can be heard when a pleural and/or pericardial effusion is present.

Tachypnoea/dyspnoea Tachypnoea/dyspnoea is a common clinical sign in cats with cardiomyopathy complicated by CHF (pul­ monary oedema and/or pleural effusion). Laboured breathing sometimes occurs acutely after a stressful event (eg, a car journey, hospitalisation or restraint), so cats suspected of having cardio­myopathy should always be examined gently and cautiously.

Limb paresis/paralysis Limb paresis/paralysis associated with ATE is often seen in cats with cardio­myopathy. Although bilateral hindlimb paresis represents the most common presen­ tation (71 per cent of all ATE cases [Smith and others 2003]), unilateral hindlimb or forelimb involvement is also possible. Thromboembolism can also potentially cause sudden death.

Cardiac arrhythmias Ventricular or supraventricular cardiac arrhythmias are frequently detected in patients with cardiomyopa­ thy. However, some forms of paroxysmal arrhythmias may not be detected during physical examination or standard electrocardiographic recording. Arrhythmias contribute to a reduction in myocardial performance and may cause syncope and sudden death.

Arterial hypotension Arterial hypotension (ie, a systolic blood pressure below 120 mmHg) has been recorded in approximately 15 per cent of cats with cardiomyopathy as a result of reduced cardiac output (Ferasin and others 2003).

Ascites

Gallop sounds

Ascites can occur in patients with right-sided CHF and are likely to be associated with ARVC, DCM or other forms of cardiomyopathy complicated by pulmonary hypertension.

Gallop sounds present another common clinical find­ ing in cats with cardiomyopathy. They are caused by audible diastolic sounds (S3 and/or S4) in the presence

Diagnosis

Fig 6: Auscultation of the thorax allows the identification of heart murmurs and gallop sounds, which are frequently detected in cats with cardiomyopathy. Although heart murmurs can sometimes be detected in apparently healthy cats, this clinical finding can also prompt an early diagnosis of myocardial disease. Echocardiographic identification of the source of the murmur is often challenging and requires sophisticated equipment, as well as experience in using Doppler techniques

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of reduced myocardial compliance (eg, myocardial hypertrophy, infiltration, fibrosis, tachycardia or a combination of these factors).

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Echocardiography Diagnosis of feline cardiomyopathy is based primarily on echocardiographic examination. Echocardio­graphic recognition of basic patterns is very intuitive but clini­ cians should be aware that incorrect conclusions may result from inexperience or intra- and interoperator variability. For example, LVH can be misdiagnosed if the M-mode cursor is incorrectly aligned or if a pap­ illary muscle or a false tendon is included in the LV measurements. Therefore, a high frame rate B-mode examin­ation with good image quality is often indicated for an accurate diagnosis of LVH. Clinicians should also remember that changes in preload and afterload can affect LV measurements. A patient’s dehydration sta­ tus can induce a ‘pseudohypertrophy’, and overzealous

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Companion animal practice fluid therapy can dilate the cardiac chambers simulating a dilated form of cardiomyopathy. The recognition and assessment of SAM is based primarily on colour flow and spectral Doppler studies, which require correct positioning, optimal settings and experienced operator skill and interpretation. Advanced echocardiographic techniques, such as TDI and myocardial strain analysis, allow further quantification of regional myocardial function and can potentially be useful in the early detection of myocardial dysfunction in cats.

Radiography Thoracic radiographs are indispensable for recognising CHF, which is characterised by cardiomegaly, engorged pulmonary veins and pulmonary oedema or pleural effusion with, in some cases, ascites. Pleural effusion and ascites can easily be detected by percussion and ultrasonography. The distribution of alveolar infiltrate can be diffuse or patchy, in contrast to the more consist­ ent caudodorsal localisation of cardiogenic pulmonary oedema seen in dogs. Cardiomegaly is not always obvi­ ous in feline cardiomyopathy, especially when there is no significant chamber enlargement (Fig 7).

Genetic tests Laboratory tests are available for Maine coon and rag­ doll cats to identify individuals with a mutation in the MYBPC3 gene. The test can be performed on EDTA blood samples or buccal swabs. However, the mutation in the two breeds is located in a different gene locus and therefore the test is not interchangeable. A posi­ tive heterozygous or homozygous result indicates that an individual may be at risk of developing HCM but it does not signify a diagnosis of HCM – this ultimately requires echocardiographic examination. Furthermore, HCM can also occur in animals that are negative on genetic testing, suggesting that there are likely to be other mutations that have not yet been identified.

Biomarkers cTn-I is a sensitive and specific marker of cardiac myo­ cyte injury and an increase in its plasma concentration, which may occur in all forms of the disease, indicates ongoing myocardial damage. This assay may provide useful information on the severity of myocardial damage and prognosis. The N-terminal pro B-type natriuretic peptide (NT-proBNP) assay is a new laboratory test that provides evidence of ongoing myocardial stress. It is highly sensi­ tive and can detect early myocardial changes associated with cardiomyopathy. A full cardiac evaluation, includ­ ing echocardiographic examination, should always be performed to identify the cause of NT-proBNP elevation and determine the proper clinical management.

Therapy At present, with the exception of dietary taurine supplementation in cats with cardiomyopathy second­ ary to taurine deficiency, there are no available treat­ ments that have convincingly demonstrated increased survival times and/or quality of life in cats with myocardial disease.

A

B

Fig 7: Thoracic radiography is an invaluable technique to identify signs consistent with congestive heart failure (CHF) before instituting treatment. (a) Dorsoventral view of a nine-year-old male neutered domestic shorthair cat presented with acute-onset dyspnoea. The cardiac silhouette is partially covered by a mild pleural effusion, the pulmonary vessels are markedly engorged and the patchy interstitial/alveolar pattern suggests the presence of pulmonary oedema. (b) Dorsoventral view of the same patient 24 hours after the administration of furosemide. The cardiac silhouette is more distinguishable and the alveolar pattern less prominent, indicating a radiographic near-resolution of the previously detected CHF

Asymptomatic cats Anecdotal reports claim that asymptomatic cats with HCM that are treated with diltiazem or beta-blockers have improved physical activity. However, randomised placebo-controlled studies are lacking to confirm this and the clinical use of these drugs in such ani­ mals has still to be proven, especially in cases that are accompanied by SAM, which could potentially ben­ efit from a reduction of dynamic outflow obstruction. Similarly, angiotensin-converting enzyme inhibitors and spironolactone have failed to demonstrate signifi­ cant improvements in cats with subclinical forms of HCM (Macdonald and others 2004, 2006, Taillefer and Di Fruscia 2006). Cats with asymptomatic forms of cardiomyopathy and echocardiographic evidence of intracavitary thrombi may benefit from antithrom­ botic prophylaxis to reduce the risk of ATE but clinical evidence has not been demonstrated clearly.

Symptomatic cats Patients presenting with acute CHF require sedation, cage rest and oxygen supplementation in addition to parenteral diuresis (ie, furosemide). Significant pleural effusion should be treated promptly by thoracocentesis. Once pulmonary oedema is clinically controlled, furo­ semide can be given orally at the lowest effective dose, to reduce the risk of prerenal azotaemia and hypoka­ laemia. The risk of hypokalaemia could be reduced by concomitant administration of potassium sparing agents, such as spironolactone, although sufficient data of its clinical efficacy in cats are not available. Diltiazem is licensed in the UK for the management of HCM due to its bradycardic, lusitropic and coronary vasodilating properties. However, its beneficial effects have not been demonstrated clearly in controlled ran­ domised clinical studies. Moreover, the licensed for­ mulation should be administered three times daily and many clients struggle to comply with this schedule. Beta-blockers have also been suggested for the treatment of feline cardiomyopathy, but the only avail­ able, and still unpublished, controlled study shows In Practice  April 2012 | Volume 34 | 204–213

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Companion animal practice that cats receiving atenolol and furosemide survived for a significantly shorter time than cats treated with furosemide alone. In the same study, cats receiving enalapril survived as long as or longer than the placebo group, although the difference was not statistically significant (Fox 2003b). Pimobendan is not licensed for use in cats, although small, uncontrolled studies seem to demonstrate an improvement in appetite and demeanour in patients with feline cardiomyopathy accompanied by systolic dysfunction. However, the pharmacokinetics of pimobendan in cats are different from those described in dogs, with a more rapid absorption and longer plasma half-life; the correct dosage and frequency of administration is unknown. A prudent approach should therefore be taken when recommending any of these drugs in addition to furosemide, for the chronic treatment of feline cardiomyopathy.

Prognosis The life expectancy of a patient depends on the form of myocardial damage and its severity, with a shorter survival time in cats with severe cardiac remodelling and clinical signs of CHF. A retrospective study conducted on a population of 127 cats with HCM shows a median survival of 194 days in symptomatic cats versus 3617 in the asymptomatic group (Payne and others 2010). In the same study, left atrial enlargement represents another negative prognostic variable. Other negative prognostic indicators include the presence of arrhythmias, gallop sounds, left atrial ‘smoke’ (spontaneous echocontrast), and reduced fractional shortening. Interestingly, the presence of SAM is associated with a longer survival time and this is possibly because it produces an audible heart murmur and allows earlier identification of the disease. Prospective longitudinal studies in progress at the time of writing and will hopefully add valuable prognostic information for cats with HCM in the near future. Other forms of cardiomyopathy carry a less favourable prognosis, with a median survival time of 132 days for RCM and 11 days for DCM (Ferasin and others 2003). Such poor prognosis is probably associated with the fact that a dilated and hypocontractile myocardium could represent the end-stage of another form of cardiomyopathy (Ferasin and others 2003).

Summary Feline myocardial disease remains a controversial topic in veterinary cardiology, despite recent discoveries on aetiology and pathophysiology that have helped the understanding of this important clinical condition. Although echocardiographic diagnosis remains extremely challenging, it is often oversimplified by non-experienced ultrasonographers, especially in cases that are complicated by dynamic outflow obstruction, which has important implications for the clinical management of patients. Hopefully, the completion and publication of some important longitudinal studies currently in progress will provide answers to the questions still arising in this clinical area.

References and further reading CESTA, M. F., BATY, C. J., KEENE, B. W., SMOAK, I. W. & MALARKEY, D. E. (2005) Pathology of end-stage remodeling in a family of cats with hypertrophic cardiomyopathy. Veterinary Pathology 42, 458-467 CONNOLLY, D. J., CANNATA, J., BOSWOOD, A., ARCHER, J., GROVES, E. A. & NEIGER, R. (2003) Cardiac troponin I in cats with hypertrophic cardiomyopathy. Journal of Feline Medicine and Surgery 5, 209-216 CONNOLLY, D. J., GUITIAN, J., BOSWOOD, A. & NEIGER, R. (2005) Serum troponin I levels in hyperthyroid cats before and after treatment with radioactive iodine. Journal of Feline Medicine and Surgery 7, 289-300 FERASIN, L. (2009a) Feline myocardial disease. 1: Classification, pathophysiology and clinical presentation. Journal of Feline Medicine and Surgery 11, 3-13 FERASIN, L. (2009b) Feline myocardial disease 2: Diagnosis, prognosis and clinical management. Journal of Feline Medicine and Surgery 11, 183-194 FERASIN, L., STURGESS, C. P., CANNON, M. J., CANEY, S. M., GRUFFYDD-JONES, T. J. & WOTTON, P. R. (2003) Feline idiopathic cardiomyopathy: a retrospective study of 106 cats (1994-2001). Journal of Feline Medicine and Surgery 5, 151-159 FOX, P. R. (2003a) Hypertrophic cardiomyopathy. Clinical and pathologic correlates. Journal of Veterinary Cardiology 5, 39-45 FOX, P. R. (2003b) Prospective, double-blinded, multicenter evaluation of chronic therapies for feline diastolic heart failure: interim analysis. (Abstract). Journal of Veterinary Internal Medicine 17, 398 FOX, P. R. (2004) Endomyocardial fibrosis and restrictive cardiomyopathy: pathologic and clinical features. Journal of Veterinary Cardiology 6, 25-31 FOX, P. R., MARON, B. J., BASSO, C., LIU, S. K. & THIENE, G. (2000) Spontaneously occurring arrhythmogenic right ventricular cardiomyopathy in the domestic cat: a new animal model similar to the human disease. Circulation 102, 1863-1870 HARE, J. (2008) The dilated, restrictive, and infiltrative cardiomyopathies. In Braunwald’s Heart Disease: a Textbook of Cardiovascular Medicine, 8th edn. Eds P. Libby, R. O. Bonow, D. L. Mann and D. P. Zipes. Elsevier Saunders. pp 1739-1762 HARVEY, A. M., BATTERSBY, I. A., FAENA, M., FEWS, D., DARKE, P. G. & FERASIN, L. (2005) Arrhythmogenic right ventricular cardiomyopathy in two cats. Journal of Small Animal Practice 46, 151-156 KOFFAS, H., DUKES-MCEWAN, J., CORCORAN, B. M., MORAN, C. M., FRENCH, A., SBOROS, V., SIMPSON, K. & MCDICKEN, W. N. (2006) Pulsed tissue Doppler imaging in normal cats and cats with hypertrophic cardiomyopathy. Journal of Veterinary Internal Medicine 20, 65-77 MACDONALD, J. E., KENNEDY, N. & STRUTHERS, A. D. (2004) Effects of spironolactone on endothelial function, vascular angiotensin converting enzyme activity, and other prognostic markers in patients with mild heart failure already taking optimal treatment. Heart 90, 765-770 MACDONALD, K. A., KITTLESON, M. D., LARSON, R. F., KASS, P., KLOSE, T. & WISNER, E. R. (2006) The effect of ramipril on left ventricular mass, myocardial fibrosis, diastolic function, and plasma neurohormones in Maine Coon cats with familial hypertrophic cardiomyopathy without heart failure. Journal of Veterinary Internal Medicine 20, 1093-1105 MEURS, K. M., NORGARD, M. M., EDERER, M. M., HENDRIX, K. P. & KITTLESON, M. D. (2007) A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy. Genomics 90, 261-264 MEURS, K. M., SANCHEZ, X., DAVID, R. M., BOWLES, N. E., TOWBIN, J. A., REISER, P. J., KITTLESON, J. A., MUNRO, M. J., DRYBURGH, K., MACDONALD, K. A. & KITTLESON, M. D. (2005) A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. Human Molecular Genetics 14, 3587-3593 PAYNE, J., LUIS FUENTES, V., BOSWOOD, A., CONNOLLY, D., KOFFAS, H. & BRODBELT, D. (2010) Population characteristics and survival in 127 referred cats with hypertrophic cardiomyopathy (1997 to 2005). Journal of Small Animal Practice 51, 540-547 PION, P. D., KITTLESON, M. D., ROGERS, Q. R. & MORRIS, J. G. (1987) Myocardial failure in cats associated with low plasma taurine: a reversible cardiomyopathy. Science 237, 764-768 RICHARDSON, P., MCKENNA, W., BRISTOW, M., MAISCH, B., MAUTNER, B., O’CONNELL, J., OLSEN, E., THIENE, G., Goodwin, J., Gyarfas, I., Martin, I. & Nordet, P. (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation 93, 841-842 Schober, K. & Todd, A. (2010) Echocardiographic assessment of left ventricular geometry and the mitral valve apparatus in cats with hypertrophic cardiomyopathy. Journal of Veterinary Cardiology 12, 1-16 SMITH, S. A., TOBIAS, A. H., JACOB, K. A., FINE, D. M. & GRUMBLES, P. L. (2003) Arterial thromboembolism in cats: acute crisis in 127 cases (1992-2001) and long-term management with low-dose aspirin in 24 cases. Journal of Veterinary Internal Medicine 17, 73-83 Taillefer, M. & Di Fruscia, R. (2006) Benazepril and subclinical feline hypertrophic cardiomyopathy: a prospective, blinded, controlled study. Canadian Veterinary Journal 47, 437-445 Wagner, T., Fuentes, V. L., Payne, J. R., McDermott, N. & Brodbelt, D. (2010) Comparison of auscultatory and echocardiographic findings in healthy adult cats. Journal of Veterinary Cardiology 12, 171-182

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