Vet. Pathol. 22: 333-337 (1985)

Endocarditis in Six Horses C. D. BUERGELT, A. J. COOLEY,S. A. HINES,and F. S. PIPERS Departments of Comparative and Experimental Pathology and Medical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Fla.

Abstract. Six horses (five males) aged three months to fourteen years had endocarditis at necropsy. Two of the horses had a clinical diagnosis of valvular endocarditis with negative blood cultures. Single or complex valvular involvement was present in five horses. One horse had non-infectious thrombi associated only with the chordae tendineae. Mitral valves were affected in four horses, and aortic semilunar valves were affected in two. Infarcts had occurred in the kidneys and the myocardium of four horses. Bacteria were isolated postmortem from the valvular vegetations of two horses; Candida parapsilosis was isolated and demonstrated morphologically in a third horse.

Although frequently encountered in other domestic animal species and man, infective endocarditis apparently is rare is horses. There are reports on isolated cases of equine vegetative valvular endocarditis found unexpectedly at n e c r o ~ s y . ~Bacteria . ~ . ~ such as Streptococcus sp and Actinobacillus equuli have been isolated from these horses.’, lo. 1 2 , l 5 Strongylus vulgaris larvae have been incriminated as a cause of aortic semilunar valvuliti~.~. l 2 The introduction of echocardiography into veterinary cardiology has facilitated the diagnosis of cardiac disorders-including those of the cardiac valves. This technique has been considered useful for the clinical diagnosis of infective endocarditis.2, l 3 This paper will summarize the pathologic findings of endocarditis in six horses necropsied between 1980 and 1983. Case Histories Most horses in this series were male thoroughbreds between three months and fourteen years of age (table I). Only two horses had a clinical diagnosis of endocarditis as evidenced by auscultation and echocardiography (horses 1 and 4). Blood cultures were negative in both horses. Horse 1 developed no fever, but arrhythmias and pulmonary edema were present. Horse 4 had fever, tachycardia, heart murmurs, and a diffuse interstitial pneumonia radiographically.The other four horses died or were sacrificed because of other ailments. Materials and Methods A standard necropsy was done on all horses. Tissues were fixed in neutral buffered 10% formalin and routinely processed for histology. Tissues were cut at 5 pm and stained with

hematoxylin and eosin (HE), Brown and Brenn, and Goodpasture’s, as well as Gomori’s methenamine silver stains. Tissues from endocardial vegetations were removed aseptically and submitted for microbiologicisolation. Microbiologic examination included aerobic and anaerobic bacterial, as well as fungal, cultures. Candida parapsilosis was isolated on Sabouraud’sagar sheets incubated at 37°C. Yeast-like colonies were confirmed by microscopy, and strain identification by germ tube formation, and by biochemical assimilation and fermentation reactions was done. Results By gross examination, isolated vegetations were found in four horses. Complex valvular involvement was present in two horses with left and right heart valve lesions. The mitral cusp or cusps were involved in four horses, the aortic semilunar valves in two, tricuspid and pulmonic valves in one each, and the chordae tendineae in two horses. The polypoid vegetations ranged between 4 x 2 x 1.5 cm and 1.5 x 1 x 1 cm (figs. 1-3). The atrial septum, as direct extension from the aortic semilunar valve vegetations, had mural endocarditis in one horse. Focal endocardial fibrosis was present in the left atrium of another horse. Ventricles were unremarkable except in horse 1 where the right ventricle was hypertrophic. Visible pale infarcts were present in one kidney of two horses and both kidneys of a third horse. A fourth horse had multiple, firm, white foci in the myocardium of the left ventricle. Microscopically, the affected valve leaflets had lost their endothelial surface and were generally thickened by granulation tissue characterized by fibroblasts, col-

333

Buergelt ef al.

334

Table I. Histories, pathological and microbiological findings in horses with infective endocarditis Horse number 1

1 1 years

2

14 years

Breed Sex TB

Clinical diagnosis

Site of endocardia1 involvement

M Valvular endocarditis; Aortic valve; right aortic insufficiency. atrium.

Culture

Infarcts

Candida parap silosis

Kidney

Mixed MC Eosinophilia and fever Chordae tendineae Not done of left ventricle. of unknown origin. Mitral and tricuspid Escherichia 1 year TB M Toxic enteritis. valves, chordae coli tendinae of right ventricle. No growth 3 StB F Valvular endocarditis. Aortic, pulmonic, months and mitral valves.

3

4

6 TB months 2 years TB

5

6 ~

Age

None None

Kidney

M Enterocolitis.

Mitral valve.

Pseudomonas aeruginosa

Kidneys

M Ventricular fibrillation.

Mitral valve.

Not done

Myocardium

-

Other major lesions Right ventricular hypertrophy; adrenal cortical adenoma; verminous endarteritis. Visceral mast cell tumor. Ulcerative colitis.

Chronic passive congestion of lung. Fibrinonecrotic entercolitis. Forelimb fracture; myocardial fibrosis.

TB = thoroughbred; StB = standardbred; M = male; MC = castrated male; F = female.

lagen, angioblasts, and newly formed small blood vessels. The vegetations were composed of large masses of fibrin and scattered groups of degenerating and viable neutrophils and lymphocytes (fig. 4). Frequently, the necrotic debris on the luminal surface of the vegetation was mineralized as evidenced by dense, basophilic, refractile material. In horse 6, long papillary projections were scattered along the valvular surface (fig. 5). Fibrin deposits were evident at the edge where the endothelium had erupted (fig. 6). The projections had a core of proliferating granulation tissue with a few inflammatory cells, and were covered by multiple layers of large, irregular, palisading, individualized, endothelial-like cells. They probably represented an attempt at endothelialization. The thrombi associated with the chordae tendineae were composed of granulation tissue and amorphous, eosinophilic, fibrillar material similar to fibrin. Occasional foci of entrapped neutrophils and platelets were seen. No agents could be demonstrated with special stains in these thrombi. Small clusters of gram-negative bacterial rods were embedded deep in the valvular lesions between inflammatory cells in horses 3 and 4 as demonstrated by bacterial stains. Massive numbers of fungal pseudohyphae were present thrughout most areas of the vegetations in horse l (fig. 7). A silver stain revealed the pseudohyphae to be long and broad, septate, and

branching; they had occasional spores (fig. 8). A few fragmented pseudohyphae were present within the atrial septa1 myocardium where most of the myocytes were replaced by granulation tissue that contained moderate numbers of neutrophils, macrophages, and hemosiderin. No infectious agents were demonstrated in the valvular vegetations of horses 5 and 6. Mild to moderate congestion and edema were observed in the lung of horses 1,2, 3 , and 4.Hemisiderinladen macrophages were present in horses 3 and 4. Renal infarctions were verified histologically in horses 1, 4, and 5 . Myocardial infarction and fibrosis were present in horse 6. In the six horses described, isolation of a n infectious agent from the valvular lesions was successful in three; in one horse, isolation was negative; in the other two horses, no isolation was attempted. Gram-negative bacteria were cultured from two horses, and a yeast in pure culture on Sabouraud's agar was isolated from a third horse. Microbiologically, the yeast which was demonstrated morphologically in the vegetation of horse 1 was identified as Candida parapsilosis because of its aerobic growth at 37"C, the morphologic features of the colonies, the negative germ tube test, and its biochemical behavior during carbohydrate assimilation and sugar fermentation tests. Horse 4 had negative microbiologic findings, but Gram-negative rods that were deeply embedded in the vegetations were found microscopi-

Equine Infective Endocarditis

335

Fig. 1: Horse 4; small vegetation associated with cusp of pulmonic semilunar valve (arrow). PA = pulmonic artery; RV = right ventricle. Bar = 1 cm. Fig. 2: Horse 4; septa1 mitral valve leaflet (arrow) and two cusps of aortic semilunar valve (double arrows) reveal cauliflowerlike vegetations of various sizes. Left atrial endocardium reveals “jet lesions.” A = aorta; MV = mitral valve; LV = left ventricle. Fig. 3: Horse 1 ; gross appearance of Cundidu purupsilosis vegetation in cusps of aortic semilunar valve (arrow). A = aorta; LV = left ventricle. Bar = 1 cm. Fig. 4: Microscopic composition of active, infective endocarditis. Wall of inflammatory cells and granulation tissue, rich in blood vessels, organizing thrombotic, necrotic material. Foci of mineralization (arrow). Fi = fibrin; G = granulation tissue; I = inflammatory cells. HE.

cally. Blood cultures taken from four horses were negative for infectious agents on repeated occasions.

horses from Florida breeding farms. In people as well as in dogs, males are affected more frequently with infective endocarditis than female^.^ Four of our horses were young, with a mean age of Discussion eleven months. Dealing with young horses and cardiac In our small series, five of the six horses were males; lesions, one has to consider cardiac malformations in four of these male horses were intact thoroughbred the clinical and pathologic differential diagnoses. In the

336

Fig. 5: Fig. 6: HE. Fig. 7: Fig. 8:

Buergelt et al.

Horse 6; mitral leaflets with villous projections on surface. HE. Horse 6; fibrin deposits at edge of leaflet endothelium. Fi = fibrin; MV

=

mitral valve matrix; En = endothelium.

Mycotic vegetation; horse I . Remnants of pseudohyphae are visible within necrotic, inflammatory exudate. HE. Morphologic appearance of C. purupsilosis in vegetation of horse 1. Giant pseudohyphae. Gomori’s methenamine.

Equine Infective Endocarditis

337

horse, nearly one-third of these malformations are ven- mon sources of infective endocarditis. Immunologic reactions may predispose valves to infection.”,’* tricular septal defects.’ I The distribution of the endocardial lesions varied in Acknowledgements our horses although there was a tendency toward left The authors thank Ms. M. R. Connelly for isolating and heart endocardial involvement. In a larger series of equine heart examinations, it was shown that the left identifying Cundida purupsilosis. We extend our thanks to side of the heart had a higher incidence of valvular the clinical faculty of the VMTH for providing the clinical data. lesions than the The aortic valve was affected most frequently, followed by the mitral valve. Tricuspid References and pulmonic valves may be affected to a lesser de1 ANDRIOLE, V.T.; KRAVETZ, H.M.; ROBERTS, W.C.; UTZ, gree.2.l 5 J.P.: Cundidu endocarditis. Clinical and pathologic studThrombotic involvement of chordae tendineae can ies. Am J Med 32:251-285, 1962 occur from extension of valvular vegetations as might 2 BONAGURA, J.D.; PIPERS, F.S.: Echocardiographic features of aortic valve endocarditis in a dog, a cow, and a horse. have been the case in horse 3 . Horse 2 only had the J Am Vet Med Assoc 182:595-599, 1983 chordae tendineae involved, and no microorganisms 3 CALVERT, C.A.: Valvular bacterial endocarditis in the dog. could be demonstrated within the thrombus. As such, J Am Vet Med Assoc 180: 1080- 1084, I982 this should be considered as a non-infectious form of 4 CRANLEY, J.J.; MCCULLAGH, K.G.: Ischaemic myocardial endocarditis. fibrosis and aortic strongylosis in the horse. Equine Vet J Stenosis due to large, polypoid growths that ob13:35-42, 1981 5 DEEGEN, E.; LIESKE,R.; SCHOON,H.: Klinische und karstructed the valvular orifice or valvular insufficiency diologische untersuchungsbefunde bei 3 deckhengsten mit that resulted from smaller vegetations are common aortenklappen insuffizienz. Tieraerztl Prax 8:2 1 1-222, functional valvular impairments. Atrioventricular valve 1980 incompetence, particularly of the mitral valve, may be 6 ELSE,R.W.; HOLMES, J.R.: Cardiac pathology in the horse. associated with regurgitation of blood, and morpholog1. Gross pathology. Equine Vet J 4: 1-8, 1972 7 ELSE,R.W.; HOLMES, J.R.: Cardiac pathology in the horse. ically may lead to friction fibrosis in the atrial endocar2. Microscopic pathology. Equine Vet J 4:57-62, 1972 dium, the so-called “jet lesions.” Focal atrial thickening 8 GOMES, J.A.C.; CALDERON, J.; LAJAM,F.; SAKURAI, H.; due to fibrosis was evident in horse 4; three other horses H.S.: Echocardiographic detection of fungal FRIEDMAN, with mitral involvement did not reveal such secondary vegetations in Cundidu purupsilosis endocarditis. Am J manifestations in the left atrium. Med 61:273-276, 1976 The incidence of human Candida spp endocarditis 9 INNES. J.R.M.: Subacute bacterial endocarditis with pulmonary embolism in a horse associated with Shigellu has been increasing in the past two decade^.'.','^ It is equirailis. Br Vet J 106:245-246, 1950 frequently encountered in drug addicts and patients 10 JUBB,K.V.F.; KENNEDY, P.C.: Pathology of Domestic which received multiple intravenous antibiotics or imAnimals, vol. 1, pp. 1 1 1-1 14, 2nd ed. Academic Press, munosuppressive therapy. Morphologically, bulky vegNew York, 1970 etations characterize the lesions on endocardial surfaces 1 1 LOMBARD, C.W.; SCARRATT, W.K.; BUERGELT, C.D.: Ventricular septal defects in the horse. J Am Vet Med Assoc in human hearts. Echocardiography is considered a 183:562-565, 1983 sensitive technique to detect the fungal vegetations in 12 MANSMANN, R.A.; MCALLISTER, E.S.; PRATT,P.W.: the absence of positive blood cultures and systemic Equine Medicine and Surgery, p. 684, 3rd ed. American embolization.’ Horse 1 had an abscess present near the Veterinary Publications, Santa Barbara, 1982 left jugular vein that ultimately eroded into the vein. 13 PIPERS,F.S.; HAMLIN, R.L.: Echocardiographic detection Acute pulmonary edema and diastolic murmurs develof cardiovascular lesions in the horse. J Equine Med Surg 3~68-77, 1979 oped two months later. Echocardiography detected aorE.; NORIEGA,E.R.; SIMBERKOFF, M.S.; tic semilunar valve irregularities. The perijugular vein 14 RUBINSTEIN, HOLZMAN, R.; RAHAL, J.J.: Fungal endocarditis: Analysis abscess might have served as the source of infection in of 24 cases and review of the literature. Am J Med 54: 33 1this horse. 344, 1975 The mode of infection for the other five horses could 15 WAGENAAR, G.; KRONEMAN, J.; BREUKINK, H.: Endocarditis in the horse. Blue Book Vet Prof 12:38-45, 1967 not be determined. Primary distant infections are com-

Request reprints from C. D. Buergelt, Box 5-103, JHMHC, University of Florida, Gainesville, FL 32610 (USA).