Conference 14 - 2009 Case: 04 20100203

Signalment:

2-year-old, male, castrated Maine coon cat (Felis catus).The cat was brought to a veterinary clinic with a history of episodic dyspnea and a 2-week history of cough. On presentation, the cat had a heart rate of 180 beats per minute (tachycardia), with a gallop rhythm on auscultation. Lung sounds were difficult to evaluate. Ultrasound examination with echoradiographs showed a mild dilatation and hypertrophy of the left ventricle, and several fibrous strands between papillary muscles of the ventricle wall and the septum wall. A mild dilatation of the left atrium could also be seen. A diagnosis of restrictive cardiomyopathy of endomyocardial fibrous type was made. The cat also had moderate hydrothorax and lung edema and the owners elected euthanasia.

Gross Description:

The heart was moderately enlarged with an elongated left ventricle, comprising a ventricular remodeling with rounded apex. Marked fibrotic structures (ventricular scar) bridged the ventricular septum (from the papillary muscle) and the free wall. The left atrium was moderately enlarged; however, the right atrium was normal and the right ventricle was only mildly hypertrophied.

Histopathologic Description:

Tissue from myocardium including endocardium: A severe thickening of the endocardium with fibrotic strands is present. These fibrotic structures are comprised of fibroblasts in a dense matrix. Lobule-like structures intermingled with parallel streaks can be seen. The extracellular matrix consists of red collagen and bluish chondroid tissue. The fibroblasts are elongated to, in some areas, round (i.e. more chondrocyte-like) in appearance. In one subendocardial area, a lipid rich tissue is found. The underlying myocardium is characterized by a diffuse, moderate interstitial fibrosis.

Morphologic Diagnosis:

Endomyocardial fibrosis with myocardial interstitial fibrosis, left ventricle, eccentric hypertrophy of left ventricle, compatible with a restrictive cardiomyopathy of endomyocardial fibrous type.

Condition:

Restrictive cardiomyopathy

Contributor Comment:

Many feline cardiomyopathies are classified as idiopathic.(2) In a retrospective study of 106 cats with cardiomyopathy, 57.5% had hypertrophic cardiomyopathy (HCM), 20.7% had restrictive cardiomyoapthy (RCM), 10.4% had dilated cardiomyopathy (DCM) and unclassified cardiomyopathy (UCM) was found in 10.4%.(2) None of the described cardiomomyopathies in that study showed the severe endomyocardial fibrosis with crossing fibrous strands in the left ventricular lumen, which characterized the heart of the Maine coon cat in this case.

Cats with RCM present with diastolic dysfunction and increased myocardial stiffness. The etiology is unknown.(3) Two basic forms of RCM in man have been reported: myocardial and endocardial RCM. These two forms are also described in the cat. The feline myocardial form, a myocardial disease with restrictive filling and severe atrial dilatation, is idiopathic. The endomyocardial form, endomyocardial fibrosis (EMF), is characterized by marked fibrosis of endocardium and endomyocardium. The etiology of EMF is not known but different backgrounds have been discussed. In human RCM, associations with hypereosinophilic syndrome, endomyocarditis or vasculitis have been suggested.(1) Many cases of human EMF have been reported from the tropics; hence a search for infectious or nutritional causes has often been pursued.

Familial HCM has been reported in Maine coon cats.(4) However, the lack of severe concentric hypertrophy and atrial dilatation is not consistent with a diagnosis of HCM in this case. An association with endomyocarditis and left ventricular endocardial fibrosis has been reported in the cat.(6) The lack of active inflammation in the present case does not rule out a viral or immune-mediated endomyocardial injury with secondary reparative fibrous tissue formation. The ultrasonographic, macroscopic and microscopic findings in the present case are compatible with a diagnosis of restrictive cardiomyopathy of endomyocardial fibrous type. This was based on the presence of many fibrous bands crossing between the papillary muscles and the septum wall. Secondary lung edema with hydrothorax had also developed.

JPC Diagnosis:

Heart: Endocardial fibrosis, diffuse, marked, with chondroid metaplasia, mild multifocal chronic endomyocarditis, interstitial edema, and myofiber disarray.

Conference Comment:

Among the cardiomyopathies of domestic animals, the feline cardiomyopathies are probably the best characterized, and include an assortment of idiopathic cardiovascular disorders. In decreasing order of prevalence, the feline cardiomyopathies are summarized below:(5)

Feline Cardiomyopathies
Classification	Key Gross Findings	Key Microscopic Findings	Summary
Hypertrophic (HCM)	Cardiomegaly with either symmetric concentric ventricular hypertrophy or asymmetric hypertrophy of the LV and a slit-like LV lumen; LA dilation; +/- atrial thrombi, multifocal ventricular fibrosis, endocardial fibrosis in the LV outflow tract	Hypertrophied myofibers with vesicular nuclei; myofiber disarray in the LVFW and IVS; diffuse interstitial fibrosis (particularly in the inner aspect of the LFFW); focal endocardial fibrosis	Most common CM in cats; autosomal dominant inheritance in Maine coon and American shorthair cats; impaired diastolic ventricular filling (due to diminished LV lumen) with usually normal systolic function; distinct from hyperthyroidsm, which also may cause concentric myocardial hypertrophy
Restrictive (RCM)	Severe endocardial thickening; mural thrombosis; marked LA dilation +/- thrombosis; thickened LVFW with diminished LV volume	Replacement of myocardium and endocardium by granulation tissue and fibrosis; histiocytic, and/or lymphoplasmacytic endomyocarditis	Includes the myocardial form and the endomyocardial form; also termed "LV endocardial fibrosis", which may be preceded by endomyocarditis, of which Bartonella sp. has been suggested as a cause; occurs primarily in older cats; impaired diastolic ventricular filling with usually normal systolic function
Dilated (DCM)	All heart chambers enlarged; ventricles dilated, flaccid, and thin-walled; atrophy of papillary muscles and trabeculae; +/- subendocardial fibrosis	Usually minor microscopic lesions; moderate myofiber hypertrophy with mild, diffuse interstitial fibrosis; +/- myofiber loss and replacement with fibrosis; usually no myofiber disarray	Distinct from and rare in comparison to taurine-deficiency myocardial failure (TDMF), which causes identical gross and microscopic lesions and systolic dysfunction resulting in bilateral congestive heart failure
Excessive moderator bands (false tendons)	Numerous pink-white bands spanning the LV lumen and papillary muscles, usually connecting the cranial and caudal papillary muscles to the IVS; LV dilated or thickened	Abnormal moderator bands composed of Purkinje cells and dense collagen covered by endothelium; LV myocyte atrophy or hypertrophy; fibrosis; intramural coronary arterial intimal thickening, medial hyperplasia, perivascular fibrosis, and luminal narrowing	Occurs in mature cats but is considered a congenital defect; clinical signs of left-sided congestive heart failure
LV = left ventricle; LVFW = left ventricular free wall; IVS = interventricular septum; CM = cardiomyopathy

Cardiomyopathy is a diagnosis of exclusion and, by strict definition, should be used only to describe idiopathic primary myocardial disease. Therefore, myocardial dilation due to taurine deficiency (i.e. taurine-deficiency myocardial failure [TDMF]) and concentric hypertrophy attributed to hyperthyroidism are distinct from dilated and hypertrophic cardiomyopathies, respectively. In cats with HCM, DCM, RCM, and myocarditis, the detection of feline panleukopenia virus genome by PCR suggests a possible causal role, but a definitive etiology for these conditions remains elusive.(5)

As alluded to by the contributor, this case may represent the chronic sequel of feline endomyocarditis, which can ultimately progress to left ventricular endocardial fibrosis, one of several idiopathic feline cardiovascular diseases grouped together clinically as RCM.(5,6) Some conference participants considered primary endocardial fibroelastosis (EFE) in the differential diagnosis; this congenital anomaly is exceedingly rare in domestic species, and is best documented in Burmese kittens, in which the condition results in microscopically detectable endocardial lymphedema at as early as one day of age. After 20 days of age, diffuse endocardial deposition of collagen and elastin is evident grossly; this may progress to involve Purkinje fibers, which undergo degeneration. Endocardial or myocardial inflammation are not features of EFE.(5)

The moderator emphasized the importance of echocardiography in correctly classifying feline cardiomyopathies clinically. Gross examination at necropsy is often less rewarding than antemortem echocardiography, and microscopic evaluation may be even less helpful, as evidenced by the overlap in microscopic findings between the various cardiomyopathies listed above and the usual paucity of significant microscopic lesions in feline DCM, specifically. A common sequel, observed in up to one third of affected cats, is unilateral or bilateral hindlimb ischemia due to iliac thromboembolism.(5,6)

References:

1. Bukhman G, Ziegler J, Parry E: Endomyocardial fibrosis: still a mystery after 60 years. PLoS Negl Trop Dis 2:e97, 2008
2. Ferasin L, Sturgess CP, Cannon MJ, Caney SMA, Gruffydd-Jones TJ, Wotton PR: Feline idiopathic cardiomyopathy: a retrospective study of 106 cases (1994-2001). J Feline Med Surg 5:151-159, 2003
3. Fox PR: Endomyocardial fibrosis and restrictive cardiomyopathy: pathologic and clinical features. J Vet Cardiol 6:25-31, 2004
4. Kittleson MD, Meurs KM, Munro MJ, Kittleson JA, Liu SK, Pion PD, Towbin JA: Familial hypertrophic cardiomyopathy in Maine coon cats: an animal model of human disease. Circulation 99:3172-3180, 1999
5. Maxie MG, Robinson WF: Cardiovascular system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., vol. 3, pp. 17-18, 36, 44-47. Saunders Elsevier, Philadelphia, PA, 2007
6. Stalis IH, Bossbaly MJ, Van Winkle TJ: Feline endomyocarditis and left ventricular endocardial fibrosis. Vet Pathol 32:122-126, 1995