How to differentiate between endocarditis and other
chronic diseases in cattle.
E.A.M. van Ampting, R. Jorritsma, S.W.F. Eisenberg, J. van den Broek
Sixty-eight cases with a chronic disease unresponsive to initial treatment were examined. Based
on the results of the post-mortem examinations 25 cows were confirmed with endocarditis. In 20
(80%) of these cases more than one heart valve was affected. Septic embolisation was found 23
(92%) times. Arcanobacterium pyogenes was the most frequently (69, 6%) isolated bacteria. The
most useful clinical tool for differentiating between the endocarditis cows and the control cows
was the auscultation of the heart. We found that endocarditis had more often a systolic murmur
on the punctum maximum of the RAV with or without a systolic murmur elsewhere. In addition,
cows with endocarditis were more often detected with signs of a pneumonia at lung auscultation
and had more often a prolonged turgor. Also cows with endocarditis more often had a decreased
hematocrit, a lower leukocyte and eosinophil count and a decreased albumin content.
Introduction
Endocarditis is defined as the inflammation of the endocardium, most commonly of one or
more heart valves.7,9,12,14 In cattle of around 1 year old and older it is a common but often undiagnosed
or misdiagnosed disease, with a rising incidence when age increases.4,7,12,16
Mostly it is secondary to a chronic infection elsewhere in the body with a prolonged
bacteraemia, such as metritis, mastitis or foot abscesses, resulting in implantation of bacteria onto the
endocardium. For individual cows, determination of the point of entry or source of infection can be
difficult as infections in other areas may have developed before or during the development of
endocardial infection, while the original infection may also have disappeared.7,13,14,16
In cows in which the disease develops, there is no evidence of preexisting valvular damage
and it is therefore assumed to be caused by an agent capable of primary invasion.13 Infection gives
rapid and severe destruction of the affected heart valve. Metastatic foci are common and occur when
pieces of the vegetation break off and are swept into the circulation. As a consequence, multiple
emboli can occlude the blood supply to parts of the heart, the kidneys, the brain, the spleen, the liver,
or the extremities and lungs resulting in infarction and the formation of abscesses. 1,7
In literature, it is described that in cattle with endocarditis the right atrial valve is affected in
the majority of the cases, followed by the left atrial valve. Also affection of more than one valve was
present in about ²/3 of the hearts of cows with endocarditis. 4,7,8,13,14 Embolic spread was found in 72%
of the animals with endocarditis send to pathology. The joints, kidneys and lungs were most
commonly affected. 7,8,14
The agents detected in most cases are Arcanobacterium Pyogenes and Streptococcus spp. A
recent study reported that an emerging pathogen in bovine valvular endocarditis is Helococcus ovis.
Using specific and appropriate culture conditions, H. ovis can be isolated in 33 % of the cases. 7,11,13,17
The standard therapy for endocarditis consists of antibiotics for 4-6 weeks and symptomatic
therapy with e.g. diuretics. 8 Because of the prolonged administration of antibiotics and the
administration of not registered diuretics the treatment is off label. The costs of the drugs in
combination with the long milk and meat withdrawal times due to the off label administration of the
medication, make the therapy in most cases economically not justified.4,13,14 Furthermore the disease
has even with this therapy a poor prognosis. This is due to the time lag before reaching an accurate
clinical diagnosis which is caused by the variability of the clinical signs, resulting in a too late start of
the therapy. 2,8,9,12,14 Even with the optimal treatment the long term survival rate is estimated at only
29%. 4,8,9 Also relapse is common when therapy is discontinued, while continued presence of a
murmur makes it difficult to decide when to end the therapy. 9,12,13,14 As a consequence, farmers
usually decide to cull cows with endocarditis. The fast majority of these cows will be declared unfit
for human consumption and transporting an animal with clinical signs of pain and cardiac failure to an
abattoir could be contrary to animal welfare regulations as well..2 Most animals with endocarditis are
therefore destroyed.
It can be concluded that cows with endocarditis should be diagnosed reliable and as soon as
possible to decide the best economic and human option for the animals and the farmers. This case
control study examines the clinical and laboratory findings in 68 cases to assess the most useful
parameters for reaching the diagnosis endocarditis within a group of cows that did not improve after
treatment.
Materials and methods
Animals
The 68 cases reviewed were seen at the Large Animal Clinic of the University of Utrecht
between February 2005 and August 2006. The included cows were all dairy cows and sold to the
university by commercial farmers for various reasons. They were to be used in the regular teaching
programme of the university. In general these cows had been treated unsuccessfully at the farm. In the
past, it was experienced that these cows had diseases like chronic bronchopneumonia, pericarditis,
traumatic reticulo-peritonitis, endocarditis, Johne’s disease or abdominal adhesions. The breed and age
distribution of the patients reflected the general bovine population seen at the Large Animal Clinic of
the University of Utrecht. The animals included were mostly born between 1998-2002. All patients
were examined by one of the attending veterinarians using a standard protocol at the day after arrival,
in order to minimize the detection of transport related abnormalities. Some of them were examined for
the second time just before they were euthanized. Cases with only minor problems of the gastrointestinal tract were excluded.
Examination
The protocol exists of a brief anamnesis with the complaint at admission, the presence of loss
of condition and earlier illnesses, a physical examination and blood and urine analysis. Posture and
gait, body condition score according to the body condition score chart from Edmonson 5 ,clinical
abnormalities on the outside, respiratory rate and type, heart rate and type, rectal temperature, colour
of the skin and mucosae, temperature of the ears and the turgor were included in the physical
examination. The examination of the cardiac system consisted of observations on the jugular and
mammary pulse and distension, the presence and location of oedema, and the auscultation of the heart.
The respiratory system was also examined and consisted of the presence and type of cough, the
presence and type of nasal discharge and the auscultation of the lungs.
For all animals blood analysis was done at the laboratory of the veterinary department of the
University of Utrecht, consisting of the hematocrit, a white blood cell count with differentiation and a
globulin spectrum. Also a glutaraldehydetest was preformed.
Finally urine analysis was preformed with urine sticks and revealed the pH and the presence of
blood and protein. The presence of protein was checked with the boiling proof of Bang. The sediment
was examined for leukocytes, erythrocytes and renal epithelial cells.
All patients were euthanized or died after investigation or treatment. A full post mortem
examination of the entire carcases was performed at the Pathology Department of the Faculty of
Veterinary Medicine, Utrecht University to assess a definitive diagnosis.
The cows were divided into 2 groups based on the pathological diagnosis. The first group
consists of the cows with the definitive diagnosis endocarditis while the control cows were in the
second group. The control animals were also all chronic ill but suffered from other conditions than
endocarditis.
Statistical analysis
Data were summarised and analysed statistically to determine the most common clinical signs
and laboratory results in endocarditis compared to the control cows. The clinical signs were condensed
into categories to allow more powerful analysis. For the statistical analysis the program SPSS 16.0
was used. To calculate if there were any significant differences between cows with and without
endocarditis, a backward stepwise binary logistic regression with likelihood ratio testing was used.
The number of 51 collected parameters involved in this research was too high in comparison
with the amount of cases involved to allow a proper statistical analysis. Therefore the parameters
belonging to each clinical or laboratory examination were included into smaller models existing of 1
category of observations. A parameter was considered significant when the P-value was smaller than
0,05. The significant parameters of each model were combined into 1 basic model. The amount of
parameters combined in this model was also too large for SPSS to make a proper analysis. The final
model was acquired by removing the least significant parameters from the basic model. Finally every
parameter, which were rejected from the basic model, was added separately once more to the logistic
regression to see if they had any influence on the final model.3
Results
Pathology results
Of the 68 cattle involved in this study 25 (36,8%) were diagnosed with endocarditis at
pathology. Only the right side of the heart was affected in 3 (12%) of the 25 cases with endocarditis,
both sides in 20 (80%) cases and only the left side in 2 (8%) cases. In 20 (80%) cases more than one
valve was affected (table 2) and in 5 (20%) cases all four of the heart valves were involved in the
process. The left atrial valve was the most commonly affected valve, being affected 20 times in the 25
cases.
Table 1: Distribution of endocarditis over the heart valves
Heart valve
Number of cases
RAV only
1
+ LAV
5
+ aortic valve
1
+ LAV and aortic
3
+ LAV + pulmonary 4
LAV only
2
+ pulmonary
1
Pulmonary only
2
+ aortic valve
1
All four of the valves
5
Percentage
4
20
4
12
16
8
4
8
4
20
Septic embolisation leading to inflammation elsewhere in the carcase was found in 23 (92%)
of the 25 animals with endocarditis send to pathology. In 8 (34,8%) of the animals more than one
organ was affected by septic emobolisation. Formation of abscesses in the lungs and evidence of a
pneumonia was present in 11 (47,8 %) carcases. Nephritis was found 10 (43,5 %) times and
(poly)arthritis 6 (26,1%) times. Also there were pathological changes found in the liver, the
myocardium, the endometrium and in the udder.
Twenty three times a bacteriological culture of the inflammation processes of the heart valves
was performed. Arcanobacterium pyogenes was with 16 (69,6%) positive cultures the most commonly
involved bacteria. Gram positive cocci were found 3 (13%) times. Arcanobacterium haemolyticum and
Clostridium were both cultured once (4,3%). One culture came back negative and one contained a mix
culture.
Statistical analysis with SPSS
A total of 58 cases were used for the statistical analysis out of a total of 76 cases examined
during the same period. Eighteen cases were not included in the statistical analysis because of missing
data, on for example urine and blood analysis. Eight of the excluded cows were diagnosed with
endocarditis. From the 58 cases included in the statistical analysis 22 (37,9 %) were diagnosed with
endocarditis.
The parameters were condensed into binary categories for the logistic regression.
Table 2: The clinical signs from the physical examination included in the final model
Parameter
Binary categories
Posture
0: normal
1: arched back
Clinical abnormalities on the outside
0: normal
1: visible chronic inflammation
Turgor
0: < 1 second
1: > 1 second
Pulse frequency
continuous variable
Quality of the pulse
0: normal
1: weak
Auscultation of the heart
0: normal or other abnormal heart sounds than
described in category 1 or 2
1: systolic murmur on at least the RAV
2: systolic murmur on one or more valves
excluding the RAV
Presence of nasal discharge
0: absent
1: present
Auscultation of the lungs
0: normal lung sounds or abnormal lung sounds
other than described in category 1
1: increased lung sounds or/and bronchial
breathing
Table 3: The included parameters from the blood and urine analysis in the final model
Parameter
Binary categories
Hematocrit
Continuous variable
Leukocyte count
Continuous variable
Juveniles count
Continuous variable
Eosinophil count
Continuous variable
Albumin count
Continuous variable
Hematurie
0: absent
1: present
Boiling proof of Bang
0: negative
1: positive
Cows with confirmed endocarditis had a delayed turgor (P- value 0,030), a systolic murmur on
one or more of the heart valves ( most often on the RAV) (P-value 0,000), increased lung sounds
or/and bronchial breathing (P-value 0,001), a decreased hematocrit (P-value 0,028), also a decreased
leukocyte and eosinophil count (P- value 0,003 and 0,004) and a decreased albumin count (P-value
0,002). (table 4) The posture was included by SPSS in the final step of the logistic regression but had a
P-value of 0,085 and thus was not significant.
Table 4: P-values for the parameters with significant differences between cattle with and
without endocarditis
Parameters
P-value
Log odds Ratio
Standard Errors
Turgor
0,030
6,592
3,890
Auscultation of the heart: 0,000
Category 1
9,774
5,012
Category 2
9,421
4,306
Auscultation of the lungs 0,001
7,989
3,917
Hematocrit
0,028
-49,992
30,310
Leukocyte count
0,003
-0,556
0,304
Eosinophil count
0,004
-1,405
0,807
Albumin count
0,002
-0,438
0,207
Given the high values of the standard errors, the estimation of the log odds ratio is not very
precise and its estimator should be interpreted with caution. However there it be concluded that
according to the log odds ratio’s a cow with endocarditis has more often (compared to other chronic
diseased cattle) a prolonged turgor, a systolic murmur on one or more of the heart valves (most often
on the right atrial valve) and evidence of a pneumonia when lung auscultation is performed.
Biochemical and hematological results will more often show a decreased hematocrit, a lower
leukocyte and eosinophil count and also a decreased albumin count for cows with endocarditis
compared to cows with other chronic diseases.
Discussion
Arcanobacterium pyogenes was the most frequently identified causative organism in this
series of cows. This might be expected given its frequent occurrence as the cause of chronic
abscessation in cattle. 7,13,17
The most useful clinical procedure for differentiating between endocarditis and other diseases
referred to the clinic was the auscultation of the heart. The murmur is systolic and located in the area
of the heart valve most involved in the inflammation process. The log odds ratio showed that this was
mostly on the right atrial valve or on more than one valve including the RAV, but the pathology data
show that de left atrial valve was affected the most. However the right atrial valve was generally
affected the most severe and apparently gives the most pronounced murmur on auscultation. The
endocarditis was located in 80 % of the cases on more than one valve. This is probably due to the
advanced stage of the disease in the cattle included and the process had already had the opportunity to
spread throughout the heart and affect more valves.
Abnormal sounds during lung auscultation were the second most significant parameter.
Evidence of an inflammatory process in the lungs was also the most common finding of secondary
thrombo-embolism at pathology. Other symptoms indicative of aerogenic pneumonia, like dyspnoea,
increased breath frequency and a cough were not found significant in this study. 12,13,15,17 Apparently
the metastatic process in the lungs related to the endocarditis, were in the cows included in the study
already large enough to be detected by auscultation. This is probably not the case for less chronic
cases.
A prolonged turgor ( > 1 second) also contributed to the diagnosis. This can be explained by
dehydration due to the chronic character of endocarditis. Given the age distribution in both groups, it
is not likely that the age of the cows might have had an effect as well.
The biochemical and hematological results display a negative correlation in the log odds ratio
for the hematocrit. Cattle with endocarditis have more often a lower hematocrit than cattle with an
other disease. This anemia is supposed to be secondary to a chronic inflammation or infection and is
mediated by the produced cytokines. 14 Given the lowered hematocrit it would be expected that cows
with endocarditis would also be paler. 4,6,12,14,15 We suggest that, as the cows in the control group
suffered from a chronic disease, their hypovolemia or dehydration gave pale mucosa and a prolonged
CRT as well and that this resulted in the fact that these parameters were not discriminative.14
It was expected that cows with endocarditis show a leukocytosis with neutrophilia in the white
blood cell count. 1,4,8,9,13,14 However in this study the leukocyte and eosinophil count have a negative
correlation in the log odds ratio. This would mean that a cow with endocarditis has a lower leukocyte
and eosinophil count than the control cows. Apparently, the illnesses of the control cows elevated the
white blood cell counts more than in the endocarditis cows, resulting in the observation that the white
blood cell count was not discriminative.
The albumin count also has a negative correlation and is lower in cows with endocarditis than
in the control cows. The decrease in albumin is explained by the increase in globulins as a
consequence of the chronic inflammation while the total protein count stays normal. That the globulin
count (specific the gamma globulins) is not significant as expected 4,6,8,9,12,13,14,16,17 is probably again
due to the chronic diseased control cows. They mostly also have an inflammation which is
accompanied by an increase in globulins.
Among the factors that were not significant in the final model are the history of a reduced
appetite with a loss of condition, which are often mentioned in other studies. 2,4,6,12,13,14,15,16,17 The
control animals were however also been diseased for a longer period of time and apparently had to the
same extent anorexia and thus loss of condition.
Earlier reported signs of pain are not significant in this final model. 2,4,7,8,12,13,15,16 Clinical
abnormalities on the outside was included in the logistic regression but had a P-value of only 0,709.
Posture was included in the final model but had a P-value of 0,085. The gait was not included and thus
not significant. These parameters did probably not attribute to the diagnosis endocarditis because of
the diseased control animals. They also suffered from diseases from which the gait becomes abnormal
and which give pain.
Recurrent periods with fluctuating fever, probably due to secondary thrombo-embolism, is
often one of the first symptoms of endocarditis and apparent in almost all cases. 1,11,12,14,15,17 Despite
these reports the temperature did in our study not significantly contribute to the diagnosis endocarditis.
This can be caused by two factors. The first is the fact that the fever is intermittent and fluctuating and
thus can be missed when the physical examination is performed once. Furthermore the control cows
often also have an elevated temperature which can diminish the effect of the temperature on the
logistic regression.
Another factor that was included in the final model but was not significant with a P-value of
0,163, was the pulse frequency. Persistent tachycardia is found in 80-90% of the reported cases in the
other studies and is also considered as one of the earliest signs after the onset of the disease.
4,6,12,13,14,16,17 Among the 43 control animals 29 % suffered from a cardiovascular disease with an
increase in pulse frequency. This factor probably diminished the effect of the pulse frequency on the
logistic regression.
Symptoms of right sided heart failure, like a pathological venous pulse and oedema that are
common in endocarditis due to the insufficiency of the affected right atrial valve were not significant.
1,2,4,8,10,12,13 This is also probably as a result from the included control cows with a cardiovascular
disease, such as pericarditis. Furthermore the animals were examined the day after arrival in the clinic.
It is possible that the disease was in a too early stage for the animal to develop right sided heart failure.
The biochemical and haematological results did not show a significant persistent proteïnurie or
hematurie, which are found commonly in cows with endocarditis due to secondary thrombo-embolism
in the kidneys.2,4,8,14,17 The parameters blood in the urine and the boiling proof of Bang were both
included in the final model but had a P-value of 0,380 and 0,553 and thus were not significant.
Nephritis was found in 43,5 % of the cases send to pathology and this percentage was probably to low
to give a significant influence of the proteinurie and hematurie on the final model.
The parameters mentioned above were apparently not distinctive for endocarditis in this study.
This however does not mean that when these symptoms are present in a diseased cow, the animal does
not have endocarditis. It is very well possible that these parameters or a combination of them are
significant in another population under other circumstances. This could in particular be the case when
the diseases encountered in the control cows are different with regard to the severity or incidence.
As this study was based on referral cases, every animal involved suffered from some kind of
chronic disease. The outcome of this study is therefore applicable to the population used and suitable
to differentiate between the chronic diseased cattle with or without endocarditis within the given
population. Some of our results were therefore unexpected and do not comply with the general opinion
on the clinical presentation of the disease. Nevertheless, we think that our results could contribute to
the diagnosis of cows with endocarditis within a group of diseased cows that did not respond to initial
treatment.
Acknowledgements
I thank Ruurd Jorritsma and Susanne Eisenberg for making it possible for me to do this study and
making available the research data. Also for all the help and encouragement offered to me in
accomplishing this study.
I thank Jan van den Broek for assisting me with the statistical analyses and all the veterinary
practitioners and staff in the pathology department for all their effort in delivering the necessary data.
References:
1. BEESON, P.B. (1979) Infective Endocarditis. Textbook of medicine 386-396
2. BEXIGA, R. (2008) Clinicopathological presentation of cardiac disease in cattle and
its impact on decision making. Veterinary record 162 575-580
3. BROEK VAN DEN, J. (2008) Binary data
4. DOWLING, P.M. (1994) Diagnosis and treatment of bacterial endocarditis in cattle.
Journal of the American Veterinary Medical Association 204 1013-1016
5. EDMONSON, A.J. (1989) A body condition scoring chart for Holstein Dairy Cows.
Journal of dairy science 72 68-78
6. ESTEPA, J.C. (2006) What is your diagnosis? Journal of the American Veterinary
Medical Association 228 37-38
7. EVANS, E.T.R. (1957) Bacterial endocarditis of cattle. Veterinary record 69 11901206
8. HEALY, M. (1996) Endocarditis in cattle. Irish Veterinary Journal 49 43-48
9. KASARI, T.R. (1989) Bacterial endocarditis Part I. Compendium on continuing
education for the practicing veterinarian 11 655-659
10. KELLY, B.J.G. (1996) Bacterial endocarditis in cattle. Irish Veterinary Journal 49
698
11. KUTZER, P. (2008) Helococcus ovis, an emerging pathogen in bovine valvular
endocarditis. Journal of Clinical Microbiology 10 3291-3295
12. MC ERLEAN, B.A. (1974) Bacterial endocarditis of cattle. Irish Veterinary Journal
28 96-97
13. POWER, H.T. (1983) Bacterial endocarditis in adult dairy cattle. Journal of the
American Veterinary Medical Association 182 806-808
14. RADIOSTITS, O.M. (2007) Veterinary medicine; A textbook of the diseases of cattle,
horses, sheep, pigs and goats 74-75 & 428-430 & 452-453
15. RAO, P.M. (1975) Vegetative endocarditis in a cow. Indian Veterinary Journal 52
956-957
16. ROUSSEL, A.J. (1989) Bacterial endocarditis Part II. Compendium on continuing
education for the practicing veterinarian 11 769-773
17. TYLER, J.W. (1991) Endocarditis in a cow. Journal of the American Veterinary
Medical Association 198 1410-1412