Infective Endocarditis

By Lisa Murphy DACVECC

Infective endocarditis (IE) is an infection of the endocardial structures which can include both the cardiac valves and mural endocardium. The disease has been infrequently reported in veterinary medicine so literature is limited to sparse retrospective studies and several case reports.

IE is uncommon in dogs and rare in cats with an estimated prevalence of 0.05-6.6% and 0.007% respectively. Over-represented breeds noted in canine cases of IE include German Shepherds, Boxers, Golden Retrievers and Labrador Retrievers with males more commonly identified with IE than females. In a recent retrospective study evaluating cats, no breed or sex predilection was identified. 

Pathogenesis

The pathogenesis of IE is likely multifactorial with many factors involved including immune system function and the integrity of the cardiac valves. It is believed that a healthy vascular endothelium is resistant to bacterial infection. Prior to colonisation of the valves, sterile and thrombotic vegetations must first develop. The vegetation is made up of platelets, fibrin, mononuclear and polymorphonuclear cells, lymphocytes and red blood cells. It is on these vegetations that circulating microorganisms can adhere to form a nidus of infection.

Early studies in people showed that differences in resting pressures in respective valves may account for why IE is more common in the higher pressure left-sided valves (mitral and aortic) compared to the lower pressure right-sided valves (tricuspid and pulmonic). 

 
 Mitral valve bacterial endocarditis in a dog.

Mitral valve bacterial endocarditis in a dog.

 

Common presentation

One of the difficulties of rapidly identifying animals with IE is the many ways the disease can present. Typically, affected animals experience vague symptoms including depression, weakness, lethargy, anorexia and intermittent lameness. In those who have significant cardiac dysfunction, symptoms of cardiac disease, including dyspnoea and coughing, may be noted. The presence of a new, previously undiagnosed heart murmur is also believed to be common in these dogs and was found in over 41% of dogs in one cohort. Since the aortic valve is commonly affected in dogs, a diastolic murmur may be noted. Cats presented with similar symptoms to dogs although a left-sided murmur was more common. In one retrospective study, pyrexia was noted in 38% of dogs. Neurological abnormalities are also common in dogs. 

Diagnosis

Thoracic radiographs can be helpful to identify secondary congestive heart failure (CHF) and pulmonary oedema but are not specific for IE. Signs of CHF were noted in 9/16 cats on thoracic radiography. In a case series of dogs with IE, thoracic radiographs revealed pulmonary oedema without concurrent left atrial enlargement in 75% of cases evaluated; this could make the radiographic differentiation between cardiac and non-cardiogenic pulmonary oedema difficult.

Echocardiography is the most common method of diagnosis. The sensitivity of echocardiography for the detection of IE is considered to be over 90% in veterinary patients. False positives are also possible as the degenerative valvular lesions from endocardiosis can be mistaken for vegetations.

Identification of possible sources of infection is recommended and typically involves microbiology (urine, blood, joint effusion). It is typically recommended that blood cultures require the sterile collection of 3-4 blood samples of 5-10ml of blood per sample from different venipuncture sites. Since the actual concentration of bacteria in the blood is low, large volumes of blood are needed to increase sensitivity. Blood culture-negative endocarditis is estimated to account for 2.5-31% of IE cases in people and up to 70% of dogs. Blood cultures may be particularly insensitive in small dogs and cats as it may not be possible to obtain adequate sample volume.

Modified Duke Criteria for Diagnosis of IE in Dogs by Sykes et al.

Modified Duke Criteria.png

Definite endocarditis was defined as fulfilment of 2 major criteria or histopathological confirmation of endocarditis. 
Possible endocarditis was defined as positive echocardiographic findings and fulfilment of 1 minor criteria, 1 major and 3 minor criteria, or 5 minor criteria.  

Treatment

Treatment of IE includes both antimicrobial therapy and management of cardiac dysfunction. Usually, culture results are not available when antibiotics are being initiated. Typically, a broad-spectrum combination to target gram positive and gram negative infections is recommended. In people, antibiotics are given intravenously for 4 to 6 weeks, which may not be feasible in veterinary patients.

Concurrent treatment of CHF is essential as 31% of canine patients with IE may present in CHF. This involves standard cardiac therapy with diuretics (e.g. furosemide) and inodilators. Although currently off-label, inodilators like pimobendan have shown to be well tolerated and prolong survival in cats with CHF with hypertrophic cardiomyopathy as well as restrictive and dilated cardiomyopathy. 

Possible sequelae

Infective endocarditis can lead to dysfunction in several other organ systems. Commonly, large amounts of immune complexes are formed as the body forms antibody titres against the invading microorganisms. Immune complexes can be deposited throughout the body, most commonly leading to polyarthritis or glomerulonephritis, both of which have been documented in dogs with IE.  Infarcts have been documented in several organs and in one case series of 4 dogs, a vascular encephalopathy developed secondary to thrombosis most commonly affecting the middle cerebral artery. 

Prevention

Antibiotic prophylaxis was previously recommended for patients at risk of IE for both dental and non-dental procedures. However conclusive benefits of this approach for the prevention of IE are lacking in human medicine. Although reports exist of IE following dental prophylaxis in dogs with myxomatous valve disease, a definitive association has not been proven. Thus antibiotic prophylaxis for this cohort of patients is not supported by current evidence.

Prognosis

The prognosis of IE is still poor. Several studies in dogs have shown a 20% survival rate in dogs with aortic valve IE tending to have a worse prognosis.  Factors associated with reduced survival included thrombocytopenia, azotaemia, and renal and thromboembolic complications. 

References

Palerme, J.S., Jones, A.E., Ward, J.L., Balakrishnan, N., Linder, K.E., Breitschwerdt, E.B. and Keene, B.W., 2016. Infective endocarditis in 13 cats. Journal of Veterinary Cardiology, 18(3), pp.213-225.

Peddle, G.D., Drobatz, K.J., Harvey, C.E., Adams, A. and Sleeper, M.M., 2009. Association of periodontal disease, oral procedures, and other clinical findings with bacterial endocarditis in dogs. Journal of the American Veterinary Medical Association, 234(1), pp.100-107.

Lombard, C.W. and Buergelt, C.D., 1983. Vegetative bacterial endocarditis in dogs; echocardiography diagnosis and clinical signs. Journal of Small Animal Practice, 24(6), pp.325-339.

Sykes, J.E., Kittleson, M.D., Pesavento, P.A., Byrne, B.A., MacDonald, K.A. and Chomel, B.B., 2006. Evaluation of the relationship between causative organisms and clinical characteristics of infective endocarditis in dogs: 71 cases (1992–2005). Journal of the American Veterinary Medical Association, 228(11), pp.1723-1734.

Peddle, G. and Sleeper, M.M., 2007. Canine bacterial endocarditis: a review. Journal of the American Animal Hospital Association, 43(5), pp.258-263