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ventricular diameter 14 mm in end-systole isconsistent with dilation and, in cases of sys-tolic dysfunction, is also accompanied byreduced FS ( 28%).9 However, a diagnosis ofCM should never be based solely on thesefindings, since increased LV myocardial thick-ness can be seen in cats that are dehydratedand/or tachycardic (so-called pseudohyper-trophy)5 and FS can vary significantly in asso-ciation with other conditions such as mitralvalve insufficiency, hyperthyroidism, sympa-thetic stimulation and over-hydration.5,10–12

Furthermore, significant overestimation ofmyocardial thickness can result from erro-

184 JFMS CLINICAL PRACTICE

CM type Two-dimensional and M-modeechocardiographic abnormalities

Doppler echocardiographicabnormalities

HCM Diastolic wall thickness ≥ 6 mm± Enlarged papillary muscles± End-systolic cavity obliteration± Increased fractional shortening± Left atrial enlargement± Right ventricular hypertrophy ± Right atrial enlargement

Prolonged IVRTMitral inflow: decreased E waveamplitude, prolonged DT andincreased A wave amplitude; E:A ratio < 1Pulmonary vein flow: reduced D wave and increased ARReduced left atrial appendix flow

HOCM As above + systolic anterior motion (SAM)

As above+ eccentric mitral regurgitation+ abrupt aortic acceleration(scimitar-like shape), consistent with dynamic obstruction

RCM Marked left atrial (or bi-atrial) dilation Absence of significant myocardialhypertrophy± Areas of increased endomyocardial echogenicity± Lesions consistent with fibrous tissue sometimes bridging the ventricular lumen

Decreased IVRTMitral inflow: increased E wavevelocity, shortened DT anddecreased A wave velocity Pulmonary vein flow: increasedAR (AR duration > transmitral Aduration)± Mitral regurgitation ± Flow turbulence caused byfibrotic lesions

DCM Increased end diastolic left ventricular diameterIncreased end systolic leftventricular diameter (≥ 14 mm)Fractional shortening ≤ 28%

Mitral inflow parameters mayvary depending on left ventricular diastolic pressureand loading conditions± Mitral regurgitation± Tricuspid regurgitation

ARVC Right ventricular dilation ± aneurism(thinner myocardial wall)Right ventricular hypokinesiaRight atrial enlargement

± Mild tricuspid regurgitation

UCM Abnormalities that do not readily fit into any of the above classifications (eg, regional myocardial abnormalities such as hypokinesia, thinner and hyperechogenic myocardium, etc)

± Mitral regurgitation± Tricuspid regurgitation

NB. A definitive diagnosis of CM should never be based solely on these echocardiographic findings since some echocardiographic parameters may vary in different physiological and pathological conditionsHCM = hypertrophic cardiomyopathy, HOCM = hypertrophic obstructive cardiomyopathy, RCM = restrictive cardiomyopathy, DCM = dilated cardiomyopathy,ARVC = arrhythmogenic right ventricular cardiomyopathy, UCM = unclassified cardiomyopathy. For explanations of IVRT, DT, E:A ratio and AR, see box on page 186

General guidelines for echocardiographic classification of feline CM

TABLE 1 neous positioning of the cursor across thepapillary muscles (which can be very difficultto avoid when papillary muscles are promi-nent). Conversely, M-mode studies can fail todemonstrate regional hypertrophy,11 and donot provide any information on abnormalblood flow, patchy fibrotic lesions or valvularinsufficiency. Finally, assessment of right ventricular (RV) morphology and function isalmost impossible on M-mode studies.

In spite of these severe limitations, there isstill a widespread tendency to concentrate onM-mode measurements and fail to notice othercardiac abnormalities that could be revealed bya more careful 2D examination, such as right-sided changes, valvular and pericardial abnor-malities, or regional reduced hypokinesis.

Two-dimensional echocardiography Two-dimensional echocardiography allowsoverall assessment of myocardial functionand identification of various phenotypicalexpressions of myocardial disease (Fig 1).Diastolic measurements of the LV myocardi-um should be taken in four different wall segments in order to identify regional hyper-trophy.11 Diagnosis of LV hypertrophy can bemade when the hypertrophic segment ( 6mm) occupies more than 50% of the LVmyocardial area.8

Papillary muscles can be measured on 2Dechocardiography; their size is generallygreater in cats with concentric myocardialhypertrophy.13

Global biventricular function should alwaysbe assessed in 2D in order to identify regionaldyssynchrony, hypokinesis or dyskinesis thatcould be related to a myocardial insult (ie,ischaemia and reparative fibrous infiltration).Paradoxical motion of the septum would suggest the presence of RV volume overloadand/or pressure overload,14 such as severe tricuspid insufficiency, pulmonary hyperten-sion, atrial septal defect or arrhythmogenicright ventricular cardiomyopathy (ARVC).

Given the limitations of M-mode studiesoutlined above, LA size should be measuredusing 2D echocardiography. The LA diameterin normal cats is approximately 10 mm, bothin short and long axis view, and, when indexed to the aortic diameter, shouldhave a ratio < 1.5.5,7 However, volume deple-tion and overzealous fluid administration canlead to significant variations in LA size andhence potentially to misinterpretation ofechocardiographic findings.5 Increased LAsize accompanied by an abnormal arching ofthe atrial septum towards the right atrium issuggestive of increased atrial pressure, whichcan lead to pulmonary venous congestion,and pulmonary oedema and/or pleural effu-sion. The presence of an echodense structure

REV IEW / Feline myocardial disease

phy and disarray, focal to multifocal or exten-sive myocyte necrosis and degeneration,interstitial fibrosis, and fibrous or fibrofattymyocyte replacement. Major or intramuralcoronary arteries can show medial and intimalthickening associated with increased connec-tive tissue elements. In some cases occlusivefibrinous thrombosis can be observed.Endomyocardial infiltrates of mononuclearcells, macrophages and occasional neutrophils(Fig 3) are often associated with symptomaticendomyocarditis in cats.17,38–42

Although some histological changes can beindicative of a particular form of CM, they areunlikely to be pathognomonic. Fibrous orfibrofatty myocyte replacement, for example,is a common sequela of the myocardialischaemia and tissue necrosis that is frequent-ly observed in all forms of cardiomyopathy.

Ante-mortem identification of infiltrativeand inflammatory changes can be obtained bytransvenous endomyocardial biopsy. How ever,use of this procedure is highly controversialdue to the associated risks of RV perforationand malignant ventricular arrhythmias.Furthermore, patchy myocardial lesions maybe missed by the random biopsy sampling.

Genetic testsGenetic mutations responsible for HCM havebeen identified both in Maine Coons43 andRagdoll cats,44 although not all Maine Coonsor Ragdolls with HCM show this particularmutation. Furthermore, the mutation in thetwo breeds is located in different regions ofthe same gene and other mutations are likelyto be identified in the future. Studies are inprogress to identify similar mutations in otherpredisposed breeds, such as the NorwegianForest Cat and Sphinx.

Genetic tests can identify individuals predis-posed to a particular mutation and may beuseful for screening programmes. However,the disease can still originate from a differentmutation that has yet to be identified.

188 JFMS CLINICAL PRACTICE

FIG 3 A variety of histopathological lesions that can be observed in feline myocardial disease.Courtesy of Dr Anibal G. Armién, University of Minnesota. CM = cardiomyopathy, HCM = hypertrophiccardiomyopathy, RCM = restrictive cardiomyopathy, DCM = dilated cardiomyopathy, ARVC = arrhythmogenic right ventricular cardiomyopathy, H&E = haematoxylin and eosin

(a,b) Interstitial fibrosis, lymphoplasmacytic infiltration and myocyte hypertrophy with fibre disarrayin the left ventricle of a cat with HCM. H&E

(c,d) Focal area of coagulation necrosis and degeneration in the atrial myocardium of a catwith HCM. H&E

(e) Severe fibrosis of the endocardium with formation of an ‘interpapillary muscle synechia’(blue area) in a cat with RCM. Interstitial fibrosis is also observed (trichromic stain); (f) Intramural coronary artery obliteration (arrowheads) in the right ventricle of a cat with CMcomplicated by arterial thromboembolism. H&E

(g) Thin and elongated myocytes with degeneration and vacuolisation and (h) subendocardialareas on a papillary muscle with myocyte hypertrophy in the left ventricle of a cat with DCM. H&E

(k,l) Necrosis and interstitial oedema in the gastrocnemiusmuscle of a cat affected by a form of CM complicated byarterial thromboembolism. H&E

(i,j) Fibrofatty infiltration (black arrows) with replacement and myocyte atrophy (red arrows) in the right ventricle of a cat with ARVC. H&E

a

c

e

g h

i j

k l

f

d

b

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JFMS CLINICAL PRACTICE 189

the heart of cats with HCM.47 Similarly, theirlevel is increased in the circulation of cats withcardiac disease.48–51 Natriuretic peptide meas-urement can be clinically useful as an initialscreening test for cats with suspected cardiacdisease. The N-terminal fragments of ANPand BNP, namely NT-proANP and NT-proBNP, are more stable, have a longer half-life and are therefore easier to analyse. Inparticular, NT-proBNP concentrations arepositively correlated with LA size and pres-sure,51 representing a useful tool for assessingcardiac disease severity and, potentially, prognosis.

The median survival time of cats with HCM that survived the first24 h after initial examination has been reported as 596–732 days(Table 2). Patients affected by ATE and concurrent myocardialdisease carry a poorer prognosis (184 days).29 Other forms ofCM carry a less favourable prognosis still, with a reportedmedian survival time of 132 days for RCM and 11 days forDCM.37 Identification of a primary cause is a critical elementinfluencing survival time since some forms of CM, such as taurine deficiency,hyperthyroidism or sustainedtachycardia, can potentiallybe corrected, withsubsequent reversal ofremodelling and resolution ofmyocardial dysfunction.

In an attempt to identify riskfactors and establish an accurateprognosis in cats with myocardialdisease, many clinical featureshave been suggested as beingsignificant.

In one study of cats with HCM,those with heart rates 200 bpmappeared to have a reducedsurvival compared with those withlower heart rates.52 However, alater study reported no statisticalassociation between heart rate andsurvival time, and whether or nottachycardia represents a negativeprognostic factor remainscontroversial.53

Clinical signs associated with CHF were found to be a negative prognostic factor in cats with HCM in tworetrospective studies.52,53 In one of these studies, LA size, age,subjective evidence of RV enlargement and the performing ofthoracocentesis were negatively associated with survival time,

but only LA size and age were significant predictors inmultivariate analyses.53 In the same study, LA and LV diameterwere also associated with a higher incidence of ATE, incontrast to the findings of a subsequent retrospective study of 127 cases of ATE.54 However, in none of the above studiesdid the authors specify the method used to measure LAdimensions. It is well documented that the M-mode method of measuring the left atrium has inherent limitations and tends

to produce different valueswhen compared with 2Devaluations.7,55 For thisreason, the associationbetween LA dimension and risk of ATE remainscontroversial.

A study of coagulation markers(thrombin–antithrombin complex,D-dimers and fibrin degradationproducts) has shown that 45% of cats with HCM are in ahypercoagulable state. However,coagulation results are notcorrelated with LA size and an association betweenhypercoagulability and the risk of thrombosis has yet to bedocumented in cats with HCM.56

A major limitation ofretrospective studies to establishprognostic factors is the inherentvariability of such studies in termsof, for example, the management

of patients following diagnosis (different clinicians may choosedifferent drugs and doses), and the severity of the cardiacdisease at presentation and at euthanasia. Additionally, criteriafor classification of myocardial disease change over time andare influenced by several subjective evaluations.

Prognosis

Genetic tests are available to identify mutations

associated with HCM in Maine Coons and Ragdoll cats.

Clinical signs associated with CHF and/or

evidence of arterial thromboembolism

represent negative prognostic indicators.

BiomarkersCardiac troponin-I (cTn-I) is a sensitive andspecific marker of cardiac myocyte injury andits plasma concentration is increased in a vari-ety of cardiac diseases, including HCM incats.45,46 An elevated cTn-I level is not pathog-nomonic for HCM, but simply indicates on -going myocardial damage, which may bepresent in any myocardial disease. However,this assay may serve as a useful adjunct tohelp determine diagnosis and/or prognosis.32

The natriuretic peptides ANP (atrial natri-uretic peptide) and BNP (brain natriureticpeptide) are found in higher concentrations in

CM type Median survival time (days)

HCM 732,52 709,53 59637

RCM 13237

DCM 1137

ARVC 30,42 9.539

UCM 92537

HCM = hypertrophic cardiomyopathy, RCM = restrictivecardiomyopathy, DCM = dilated cardiomyopathy, ARVC = arrhythmogenic right ventricular cardiomyopathy, UCM = unclassified cardiomyopathy

Median survival times of catswith CM surviving the first 24 hafter initial examination

TABLE 2

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190 JFMS CLINICAL PRACTICE

Clinical management of thesymptomatic patientIdeally, treatment of feline CM should be aimedat resolving all the underlying pathogeneticmechanisms of the disease, such as diastolicand systolic dysfunction, dynamic outflowobstruction, ischaemia, arrhythmias, neurohor-monal activation and hypercoagulability status.In reality, with the exception of taurine supple-mentation in cats with taurine-deficient DCM,such ideal treatment is not available and nodrug at present has convincingly demonstratedits ability to improve survival and/or quality oflife in cats with myocardial disease.

Diuretics and other treatments for CHFIn practice, the patient presenting with clinicalor radiographic signs of CHF should be treat-ed accordingly. In cases of acute respiratorydistress, stress should be minimised and cagerest and oxygen supplementation should beinstituted promptly. Pulmonary oedema isgenerally controlled by intravenous adminis-tration of furosemide q 4–6 h until a normalrespiratory rate is achieved. Dyspnoea sec-ondary to pleural effusion can be successfullymanaged by thoracocentesis. Sedative med-ication with acepromazine and butorphanolmay help to alleviate the respiratory distress.In extreme cases, where the patient does notrespond to acute diuresis, airway suctioningand mechanical ventilation can be consid-

Whether or not an asymptomatic cat with CMshould be treated is controversial. Anecdotalreports claim improvement in physical activitylevels in asymptomatic cats with HCM treated

with diltiazem or β-blockers.28 In addition, arecent pilot study has demonstrated a possible

reduction in myocardial damage in cats with compensatedHCM following dailyadministration ofatenolol, as suggestedby a significantreduction in circulatingcTn-I.57 However,randomised placebo-controlled studies arestill lacking and clinicalbenefits of diltiazem or β-blockers in asymptomatic cats haveyet to be proven.

ACE inhibitors have also been advocated in cases of HCM,both in asymptomatic and symptomatic cats.58 In thatparticular retrospective study, significant changes in cardiacdimensions were identified by echocardiography, together withan improvement in life expectancy, after administration ofenalapril. Unfortunately, recent prospective, controlled studieshave failed to demonstrate significant effects of ACE inhibitors(benazepril and ramipril) in cats with subclinical HCM.59,60

The potassium-sparing agent spironolactone has shown

anti-remodelling properties in human patients withasymptomatic cardiac disease, as well as in patients with mild CHF (NYHA class I and II).61 It is not unreasonable tohypothesise that spironolactone may produce a similar effectin cats with asymptomatic CM, although controlled clinicalstudies would be necessary to confirm this. Regrettably, arecent study failed to demonstrate improvement of diastolic

function and LV mass in Maine Coon cats with HCM treated withspironolactone for 4months. Furthermore, in that study, one-thirdof the treated catsdeveloped severeulcerative facial

dermatitis.61 However, to the best of the author’s knowledge,this side effect has never been reported in Europe.

Cats with asymptomatic forms of CM but withechocardiographic evidence of intracavitary thrombi,spontaneous echo contrast or severe LA dilation may benefitfrom antithrombotic prophylaxis to reduce the risk of ATE. This could theoretically be achieved by administering low-doseaspirin,54 clopidogrel62 or a combination of the two drugs,although such combination has not shown clinical benefit inhumans.63 However, results of controlled prospective studies arenecessary to prove the prophylactic efficacy of these treatments.

The asymptomatic pat ient : a treatment di lemma

At present, there is no convincing evidence of

clinical benefits associated with early

pharmacological interventions in asymptomatic

cats affected by myocardial disease.

ered.28 Once pulmonary oedema is sufficient-ly controlled, furosemide can be given orallyat the lowest effective dose.

A similar approach should be taken inchronic and non-acute cases in order to reducethe negative side effects of diuresis, includingreduced ventricular preload, hypotension,prerenal azotaemia and hypokalaemia, whichcan predispose to anorexia and severe ventric-ular arrhythmias. The risk of hypokalaemiacould be reduced by concomitant administra-tion of a potassium-sparing agent, such asspironolactone, although sufficient data ofclinical efficacy in cats are not available.

Calcium channel blockersCalcium channel blockers have been advocatedas an effective treatment for symptomatic felineHCM for many years.64 Diltiazem has a lessereffect on the systemic vasculature and inotropicstate than verapamil, and it is generally the calcium channel blocker of choice for the treat-ment of feline HCM. The claimed beneficialtherapeutic effects of diltiazem are due to itspositive lusitropic and coronary vasodilatingproperties and include increased LV filling,reduced heart rate, increased venous oxygentension, improved echocardiographic parame-ters and resolved radiographic abnormalities.64

However, due to its pharmacokinetics, dilti-azem needs to be administered every 8 h, andmany clients struggle to comply with this dos-

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JFMS CLINICAL PRACTICE 191

ing regimen, administering the drug only onceor twice daily. Unfortunately, the administra-tion of the extended release formulation isaccompanied by significant side effects.65

Beta-blockersBeta-blockers have also been suggested as a use-ful treatment for feline CM since they can pro-vide heart rate and arrhythmia control, relieveLVOT obstruction and lessen myocardial oxy-gen demand.28 Atenolol, a selective β-1 agonist,is generally preferred over other β-blockers (ie,propranolol) because it reduces the risk of bron-chospasm. Also, it can be administered onlyonce or twice daily, versus the recommendedthree times daily administrations of propranolol.

Interim results of a prospective, double-blind, multicentre, controlled study compar-ing the clinical efficacy of atenolol, diltiazemand enalapril in cats with diastolic heart fail-ure revealed that cats receiving atenolol andfurosemide survived for a significantly short-er time than cats treated with furosemide

alone.66 Similarly, survival rates for patientsreceiving diltiazem were poorer than for catson furosemide alone, while cats in theenalapril group did as well or better than theplacebo group. However, these differenceswere not found to be statistically significant.66

Therefore, a prudent approach should betaken when recommending any of thesedrugs, in combination with furosemide, forlong-term treatment of feline CM.

Taurine supplementationTaurine-deficient DCM cases can be successful-ly treated with taurine supplementation, inaddition to supportive therapy to control theclinical signs of CHF. Echocardiographic evi-dence of improved systolic function is general-ly seen within 6 weeks of supplementation.67

Inotropic drugsCats with echocardiographic evidence of sys-tolic dysfunction not related to taurine deficien-cy may benefit from positive inotropic drugs.

Drug Trade name Class Pharmacological action Dose

Enalapril70 Enacard (Merial) ACE inhibitor Promotes veno- and arteriodilation (reduced ventricular preload and afterload); decreases Na andwater retention; depresses sympathetic activation

0.25–0.5 mg/kg PO SID or BID

Benazepril70 Fortekor (Novartis)Benazecare(Animalcare)

ACE inhibitor As above 0.25–0.5 mg/kg PO SID or BID

Ramipril71 Vasotop (IntervetSchering-Plough)

ACE inhibitor As above 0.5 mg/kg PO SID

Imidapril72 Prilium (Vétoquinol) ACE inhibitor As above 0.25 mg/kg PO SID

Diltiazem72 Hypercard* (Dechra) Benzothiazepine(Ca channel blocker)

Reduces heart rate and myocardial contractility;vasodilation (cardiac vessels and peripheral arteries)

10 mg/cat PO TID

Atenolol72 Atenolol (non-proprietary)

β1 receptor selectiveantagonist (β-blocker)

Reduces heart rate and myocardial contractility;induces mild vasodilation

6.25–12.5 mg/cat PO SID

Pimobendan72 Vetmedin (BoehringerIngelheim)

Ca sensitiser andPDEIII inhibitor

Induces myocardial contractility and vasodilation(inodilator). Promotes myocardial relaxation (positive lusitrope)

0.1–0.3 mg/kg PO BID

Furosemide†72 Dimazon (IV)†(Intervet Schering-Plough)Frusemide (PO)†(non-proprietary)Frusecare (PO)†(Animalcare)Frusedale (PO)†(Dechra)

Loop diuretic Promotes diuresis by inhibiting Na reabsorption 0.5–2 mg/kg PO or IV SID to TID

Spironolactone72 Prilactone (Ceva) Potassium-sparingdiuretic

Promotes diuresis by inhibiting aldosterone action.Might reduce cardiac remodelling

2–4 mg/kg PO SID

Taurine71 Taurine (non-proprietary)

Amino acid Essential in cats for myocardial mechanical function 125–250 mg PO BID

Aspirin71 Aspirin(non-proprietary)

NSAID Inhibition of platelet aggregation 81 mg/cat q 3 d or5 mg/cat q 3 d

Clopidogrel71 Plavix(Sanofi-Aventis)

Antiplatelet drug Inhibition of platelet aggregation 18.75 mg/cat SID

*Licensed in the UK for the clinical management of feline primary HCM, †Licensed in the UK for the clinical management of feline CHF, PO = orally, IV = intravenously, SID = once daily, BID = twice daily, TID = three times daily, q 3 d = every three days, PDEIII = phosphodiesterase III,NSAID = non-steroidal anti-inflammatory drug

Drugs commonly used in the clinical management of feline myocardial disease TABLE 3

194 JFMS CLINICAL PRACTICE Available online at www.sciencedirect.com

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