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J Vet Intern Med 2003;17:588592

Cardiac Amyloidosis in a Horse


Yvette S. Nout, Kenneth W. Hinchcliff, John D. Bonagura, Kathryn M. Meurs, and Tracey L. Papenfuss

ardiac failure in horses usually occurs secondary to


congenital cardiac disease, pericarditis, or insufficiency of the mitral, aortic, or tricuspid valves.1,2 Heart failure
as a result of primary myocardial disease is unusual in horses.
Myocarditis and dilated cardiomyopathy (DCM) are 2
types of myocardial disease recognized in horses. The inciting cause of myocarditis often is undetermined, but documented etiologies include envenomation3; bacterial, viral,
fungal,4 or parasitic infections5; and thromboembolic disease caused by these organisms.1,6 DCM is a subacute or
chronic disease of the ventricular myocardium that occurs
without anatomic valvular disease, congenital malformations of the heart or vessels, or pulmonary disease. The
etiology of DCM often is undetermined (idiopathic DCM),
but conditions associated with secondary DCM include
myocarditis, ionophore intoxication, vitamin E-selenium
deficiency, relentless tachycardia, and neoplasia.1,7 Dilated
cardiomyopathy, characterized by left ventricular dilatation
and decreased shortening fraction, is the only cardiomyopathy of known clinical relevance in horses. To our knowledge, neither restrictive nor hypertrophic cardiomyopathies
have been reported in horses.
The various forms of cardiomyopathy are distinguished
based on morphologic and echocardiographic criteria. Restrictive cardiomyopathy (RCM) in human patients is characterized by infiltration of the heart and impaired ventricular filling.8,9 Whereas RCM is the least common of the 3
cardiomyopathies in humans, it is associated with the highest mortality.911 Infiltrative disease of the myocardium, typically from amyloidosis, represents the most common cause
of RCM in humans.10 Although cardiomyopathy because of
infiltrative disease is a well-recognized entity in human
medicine, in the veterinary literature, cardiomyopathy associated with infiltrative disease has been reported only in
a cat with lymphoma12 and in cats with extensive endomyocardial fibrosis.13,14 Amyloidosis as a cause of RCM
and congestive heart failure in the horse has, to the authors
knowledge, not been reported thus far.
A 16-year-old Thoroughbred gelding was presented to
The Ohio State University Veterinary Teaching Hospital for
difficulty swallowing, recurrent episodes of apparent esophageal obstruction, weight loss, and anorexia of approxiFrom the Department of Veterinary Clinical Sciences (Nout, Hinchcliff, Bonagura, Meurs) and the Department of Veterinary Biosciences
(Papenfuss), College of Veterinary Medicine, The Ohio State University, Columbus, OH.
Reprint requests: Yvette Nout, DVM, Department of Veterinary
Clinical Sciences, College of Veterinary Medicine, The Ohio State
University, 601 Vernon L Tharp Street, Columbus, OH 43210-4007;
e-mail: nout.1@osu.edu.
Submitted November 2, 2002; Revised January 13, 2003; Accepted
January 13, 2003.
Copyright q 2003 by the American College of Veterinary Internal
Medicine
0891-6640/03/1704-0018/$3.00/0

mately 2 weeks duration. Within a 2-week period the horse


had 2 episodes of feed discharge from the nares. Veterinary
evaluation after the 2nd episode identified an irregular heart
rhythm. Endoscopy of the proximal esophagus at that time
did not disclose abnormalities. The horse was used for lower level indoor riding and was housed with 33 other horses.
Previous medical problems included enterocolitis 9 months
before presentation, from which the horse made an uneventful recovery.
On presentation, the horse was quiet, but attentive and
responsive. It was thin (body condition score: 2 out of 9),
had ventral edema, and was tachycardic (88 beats/min).
Cardiac auscultation identified an irregularly irregular heart
rhythm, which was confirmed by electrocardiography as
atrial fibrillation. No murmurs were detected, but the heart
sounds on the left side were muffled. The peripheral pulse
was difficult to detect and varied in intensity. Jugular pulses
were visible in the midcervical region. Carotid arterial
blood pressure varied with the arrhythmia, but was not abnormally high (,140 mm Hg systolic). Rectal temperature
and respiratory rate were within normal limits.
Hyperglobulinemia (7.6 g/dL; reference range, 2.64.0
g/dL) with slightly high fibrinogen concentration (360 mg/
dL; reference range, 100300 mg/dL) and slightly increased concentration of troponin I (0.17 ng/mL; reference
range, ,0.15 ng/mL) were present. Serum albumin concentration was within normal limits (2.8 g/dL; reference
range, 2.33.9 g/dL). Thoracic radiographs disclosed generalized enlargement of the cardiac silhouette with enlargement of the left atrium and dilatation of the cranial and
caudal venae cavae. The pulmonary vasculature was prominent, with vessels of increased diameter. A diffuse interstitial infiltrate was present throughout the lung fields. Thoracic ultrasonographic examination identified a small
amount of pleural effusion. Abdominal ultrasonography
disclosed distention of the hepatic veins.
Cardiac ultrasonographic examination identified a small
amount of pericardial effusion. The left ventricular diameter
at the end of systole was within normal limits (7.3 cm;
reference range, 7.4 6 0.7 cm)7; however, at the end of
diastole, it was slightly smaller (9.4 cm) than what has been
reported (reference range, 11.9 6 0.7 cm).7 The interventricular septum was thickened at the end of diastole (5.3
cm; reference range, 3.1 6 0.6 cm)7 and during systole (6.0
cm; reference range, 4.8 6 0.7 cm).7 The left ventricular
free wall was thickened at the end of diastole (4.6 cm;
reference range, 2.9 6 0.5 cm)7 and at the peak of systole
(5.2 cm; reference range, 4.5 6 0.6 cm).7 The marked thickening of the myocardium was concentric and relatively
symmetric (Figs 1a, 2). The myocardium of the left and
right ventricular free walls subjectively was hyperechoic
(Figs 1a, 2). The left atrium was rounded and dilated (15.6
cm; reference range, 12.8 6 0.8 cm)1 (Fig 1a). The diameter of the pulmonary artery was larger than that of the
aortic root, consistent with pulmonary artery dilatation (Fig
1b). Subjectively, the right atrium and the right ventricle

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Cardiac Amyloidosis in a Horse

Fig 1. (a) Two-dimensional echocardiographic image of the left atrium (LA), mitral valve, and dorsal left ventricular cavity (LV) obtained
from the left thorax. The left ventricular free wall (LVW) is thick and
hyperechoic. The interventricular septum (IVS) in the far field is less
echogenic owing to attenuation of echoes in the far field. (b) Twodimensional echocardiographic image at the cardiac base showing portions of the right atrium (RA), the aortic root (AO), and the main
pulmonary artery (PA) and right branch (RPA). The PA is dilated
(arrow) relative to the aorta, a finding compatible with pulmonary
hypertension.

were dilated (Fig 1b). Overall, left ventricular function was


reduced and fractional shortening was 22% (reference
range, 3744%)1,7 (Fig 2). No abnormalities of the valves
were detected, and mild mitral and tricuspid regurgitation
were observed. Marked spontaneous contrast was identified
in the right atrium and right ventricle (Fig 2).
Atrial fibrillation and biventricular heart failure by primary hypertrophic or infiltrative cardiomyopathy were diagnosed on the basis of clinical findings and the results of
radiography and echocardiography. Pulmonary hypertension secondary to left-sided congestive heart failure was
suspected. Because of the poor prognosis associated with
cardiomyopathy and congestive heart failure in the horse

589

and the severity of the disease, the owners elected euthanasia.


The findings on postmortem examination were consistent
with cardiomyopathy. The heart was enlarged (6.3 kg; animals body weight: 557 kg) and had a valentine appearance with proportional enlargement of all chambers.
Bilateral atrial and ventricular hypertrophy were apparent
grossly. Microscopic examination of the cardiac muscle
identified moderate multifocal fibrosis and myocyte atrophy
and hypertrophy. Multifocally throughout the myocardium,
individual cardiac myocytes and capillary walls were prominently outlined by hyalinization of the basement membrane, whereas other areas appeared less affected (Fig 3).
Special stains demonstrated that hyalinization was not due
to fibrosis or deposition of basement membrane. Amyloid
deposition was confirmed by fluorescence under ultraviolet
light on thioflavin-Tstained sections (Fig 4) and orange
deposits that had apple-green birefringence under polarized
light on Congo redstained sections. After treatment with
potassium permanganate, the apple-green birefringence remained detectable, which suggested the amyloid was of the
light chain immunoglobulin (AL) type. Areas of marked
amyloid infiltration were associated with cardiac myocytes
that were fragmented and smaller and paler than normal.
The cardiac lesions were severe and considered to be the
cause of this horses cardiac disease. Microscopic examination of Congo redstained tissue specimens under polarized light demonstrated marked multifocal amyloid deposits
in the mucosa and submucosa of the stomach, esophagus,
duodenum, jejunum, and colon. Inflammatory disease was
not observed in any of the tissues examined.
This horses clinical findings were consistent with biventricular heart failure from ventricular dysfunction, atrial
fibrillation, and pulmonary hypertension. Clinical signs
characteristic of congestive heart failure in horses are attributable to reduced cardiac output and increased ventricular filling pressures and include tachycardia, weight loss,
weakness, exercise intolerance, ataxia, weak arterial pulses,
and congestion of the systemic and pulmonic circulation.
Pulmonary hypertension can be a consequence of left-sided
heart failure. Pulmonary edema from left-sided heart failure
was suggested from the interstitial pattern on thoracic radiographs. Radiographic evidence of pulmonary venous
congestion also might be present,1 as seen in this case.
Signs of right-sided heart failure include peripheral venous
distention, abnormal pulsations of the jugular vein, dependent edema, and peritoneal and pleural effusion.
In this horse, cardiac failure was attributed to infiltrative
cardiomyopathy secondary to systemic amyloidosis. Clinical signs, clinicopathologic data, and histopathology were
not indicative of an infectious cause of the myocardial disease. Cardiac troponin I is involved in the actin-myosin
interaction during muscular contraction, and an increased
concentration is considered a very sensitive and specific
marker of myocardial damage in humans and other mammalian species.15,16 The mild increase of troponin I concentration in this horse was consistent with a chronic or degenerative myocardial disease, rather than myocarditis.
Echocardiography disclosed a symmetric thickening (apparent hypertrophy) of both ventricles and a hypokinetic
left ventricular free wall without evidence of an underlying

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Nout et al.

Fig 2. M-mode echocardiogram recorded across the ventricles. Structures observed from near to far field are the right ventricular free wall
(RVW), right ventricle (RV), interventricular septum (IVS), left ventricle (LV), and left ventricular wall (LVW). Global LV systolic function is
mildly reduced. The IVS and LVW are thickened. The IVS also appears hyperechoic (relative to the RVW). The LVW in the far field is less
echogenic owing to attenuation of echoes in the far field. The right ventricle contained spontaneous echocontrast. (Reference lines indicate 5 cm
depth and 0.5 seconds duration.)

structural heart disorder such as valvular disease or cardiac


malformation. This finding is in contrast to the echocardiography findings in horses with DCM, in which ventricular
dilatation and marked hypokinesis are the most remarkable
findings.1 The other primary diagnostic considerations were
hypertrophic cardiomyopathy or hypertensive heart disease,

but hypertrophic cardiomyopathy has not been reported in


horses and arterial blood pressure was not increased in this
horse. Atrial fibrillation was most likely due to the associated atrial enlargement.1,17
Amyloidosis is a group of diseases characterized by the
extracellular deposition of amyloid in tissues. Amyloid de-

Fig 3. Hematoxylin and eosinstained myocardial tissue from the interventricular septum viewed at a power of 403. Large arrowheads indicate
hyalinization around individual cardiac myocytes. Small arrowheads indicate hyalinization around blood vessels and capillaries. The apparent
areas of hyalinization are amyloid deposits, as demonstrated after viewing Congo redstained sections under polarized light (not shown).

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Cardiac Amyloidosis in a Horse

591

Fig 4. Thioflavin-Tstained myocardial tissue under ultraviolet light, demonstrating the fluorescence of amyloid deposits around individual
cardiac myocytes.

posits are homogenous hyaline protein infiltrates that cause


distortion of normal visceral architecture and can lead to
functional impairment of organs.18,19 The classification of
the various types of amyloidosis is based on the precursor
protein that forms the fibrillar deposit. Most cases of amyloidosis in animals are idiopathic, but appear to be of the
reactive systemic or secondary type, in which amyloid apoprotein (AA) is derived from serum amyloid A (SAA) protein. Less commonly seen are the immunocytic or primary
and hereditary amyloidoses.20 In immunocytic amyloidosis,
unstable monoclonal immunoglobulin light chains, produced by a plasma cell dyscrasia, lead to the formation and
deposition of AL fibrils.20
Both systemic and localized or organ-limited forms of
amyloidosis exist in humans and various animal species.
Amyloidosis in horses is most commonly of the cutaneous
form, although conjunctival and nasal amyloidosis have
been reported.2124 The amyloid in these localized forms of
equine amyloidosis appear to be primarily of the AL type,
whereas systemic amyloidosis generally is of the AA type.23
These observations are in contrast to the systemic amyloidosis described in this horse, which appeared to be of the
AL type. Systemic or visceral amyloidosis is rare in horses,25 with the exception of amyloidosis seen in horses that
are used for serum production.19,23 The amyloidosis seen in
these animals is attributed to increased synthesis of SAA
after chronic antigenic stimulation.26 However, increased
SAA concentration alone is not sufficient for the development of reactive amyloidosis, and other factors are believed
to be important in the pathogenesis of this disease.19
Amyloid is recognized microscopically by the green bi-

refringence noticeable when viewing Congo redstained


tissue specimens under polarized light.27 AA and AL amyloid can be distinguished by potassium permanganate
treatment of the tissue sections; AL amyloid is resistant,
but AA amyloid is oxidized with subsequent loss of its
Congo red stain.18,20 The specific type of amyloid fibril can
be identified by light and electron microscopy of labeled
antibodies by immunogold staining.28
In this horse, amyloidosis affected the entire gastrointestinal system, but no clinical signs of gastrointestinal disease
were present, and serum albumin concentration was within
normal limits. The association between previous enterocolitis and amyloidosis may be no more than temporal. The
clinical relevance of the visceral amyloidosis is unclear. The
problem of recurrent choke in this horse was not investigated, and the clinical significance of the amyloid deposits
that were present in the esophagus remains unknown. However, this association between choke and esophageal amyloidosis may be a causal association.
Cardiac involvement is common in humans with systemic AL disease, being the major presenting clinical manifestation in 20% of patients.29 Amyloidosis is the main cause
of infiltrative cardiomyopathy in humans, other causes being neoplastic processes and inherited disorders leading to
accumulation of abnormal metabolic products.30 Humans
with cardiac amyloidosis generally present with clinical
signs of congestive heart failure, especially right-sided because of RCM, characterized by diastolic dysfunction of the
heart. Diastolic evaluation of the left ventricle by Doppler
echocardiography was not undertaken in this horse but
might have been instructive. However, the tachycardia and

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loss of atrial filling function would have made this evaluation difficult. The most important differential diagnoses in
human medicine are RCM that is due to pericarditis and
hypertrophic cardiomyopathy. The diagnosis is made accurately in the majority of cases using current diagnostic
modalities, including Doppler echocardiography, computed
tomography, and the antemortem utilization of biopsy techniques.30,31
This report describes a case of heart failure from infiltrative cardiomyopathy caused by amyloidosis, which has
thus far not been reported in the horse. Careful echocardiography is indicated in horses with cardiac failure to determine the cause of the disease, although prognosis remains poor. The etiology of the amyloidosis in this horse
remains unknown.

References
1. Marr CM. Cardiology of the Horse. London: WB Saunders;
1999:10, 102, 298311.
2. Davis JL, Gardner SY, Schwabenton B, Breuhaus BA. Congestive heart failure in horses: 14 cases (19842001). J Am Vet Med
Assoc 2002;220:15121515.
3. Hoffman A, Levi O, Orgad U, Nyska A. Myocarditis following
envenoming with Vipera palaestinae in two horses. Toxicon 1993;31:
16231628.
4. Peet RL, McDermott J, Williams JM, Maclean AA. Fungal myocarditis and nephritis in a horse. Aust Vet J 1981;57:439440.
5. Cranley JJ, McCullagh KG. Ischaemic myocardial fibrosis and
aortic strongylosis in the horse. Equine Vet J 1981;13:3542.
6. Bonagura JD, Reef VB. Cardiovascular diseases. In: Reed SM,
Bayly WM, eds. Equine Internal Medicine. Philadelphia, PA: WB
Saunders; 1998;290370.
7. Reef VB. Equine diagnostic ultrasound. Philadelphia, PA: WB
Saunders; 1998:222, 249254.
8. Keren A, Popp RL. Assignment of patients into the classification
of cardiomyopathies. Circulation 1992;86:16221633.
9. Ammash NM, Seward JB, Bailey KR, et al. Clinical profile and
outcome of idiopathic restrictive cardiomyopathy. Circulation 2000;
101:24902496.
10. Artz G, Wynne J. Restrictive cardiomyopathy. Curr Treat Options Cardiovasc Med 2000;2:431438.
11. Felker GM, Thompson RE, Hare JM, et al. Underlying causes
and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 2000;342:10771084.

12. Brummer DG, Moise NS. Infiltrative cardiomyopathy responsive to combination chemotherapy in a cat with lymphoma. J Am Vet
Med Assoc 1989;195:11161119.
13. Stalis IH, Bossbaly MJ, Van Winkle TJ. Feline endomyocarditis
and left ventricular endocardial fibrosis. Vet Pathol 1995;32:122126.
14. Fox PR. Feline cardiomyopathies. In: Fox PR, Sisson DD, Moise NS, eds. Textbook of canine and feline cardiology, 2nd ed. Philadelphia, PA: WB Saunders; 1999:641645.
15. La Vecchia L, Mezzena G, Zanolla L, et al. Cardiac troponin I
as diagnostic and prognostic marker in severe heart failure. J Heart
Lung Transplant 2000;19:644652.
16. Sleeper MM, Clifford CA, Laster LL. Cardiac troponin I in the
normal dog and cat. J Vet Intern Med 2001;15:501503.
17. Reef VB, Levitan CW, Spencer PA. Factors affecting prognosis
and conversion in equine atrial fibrillation. J Vet Intern Med 1988;2:
16.
18. Husby G. Equine amyloidosis. Equine Vet J 1988;20:235238.
19. DiBartola SP, Benson MD. The pathogenesis of reactive systemic amyloidosis. J Vet Intern Med 1989;3:3141.
20. Jubb KVF, Kennedy PC, Palmer N. Pathology of Domestic Animals, 4th ed. San Diego, CA: Academic Press; 1993:484486.
21. Stunzi H, Ehrensperger F, Wild P, Leemann W. Systemic cutaneous and subcutaneous amyloidosis in the horse. Vet Pathol 1975;12:
405414.
22. Shaw DP, Gunson DE, Evans LH. Nasal amyloidosis in four
horses. Vet Pathol 1987;24:183185.
23. Van Andel AC, Gruys E, Kroneman J, Veerkamp J. Amyloid
in the horse: A report of nine cases. Equine Vet J 1988;20:277285.
24. Mould JR, Munroe GA, Eckersall PD, et al. Conjunctival and
nasal amyloidosis in a horse. Equine Vet J Suppl 1990;10:811.
25. Hayden DW, Johnson KH, Wolf CB, Westermark P. AA amyloid-associated gastroenteropathy in a horse. J Comp Pathol 1988;98:
195204.
26. Hawthorne TB, Bolon B, Meyer DJ. Systemic amyloidosis in a
mare. J Am Vet Med Assoc 1990;196:323325.
27. Glenner GG. Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts). N Engl J Med 1980;302:12831292.
28. Khan MF, Falk RH. Amyloidosis. Postgrad Med J 2001;77:686
693.
29. Buxbaum JN, Genega EM, Lazowski P, et al. Infiltrative nonamyloidotic monoclonal immunoglobulin light chain cardiomyopathy:
An underappreciated manifestation of plasma cell dyscrasias. Cardiology 2000;93:220228.
30. Braunwald E. Heart disease: A textbook of cardiovascular medicine, 4th ed. Philadelphia, PA: WB Saunders; 1992:14161419.
31. Willerson JT, Cohn JN. Cardiovascular medicine, 2nd ed. Philadelphia, PA: Harcourt; 2000:10821086.