Cardiovascular

Bacterial endocarditis

Bacterial endocarditis is an uncommon, life-threatening cardiac disorder in horses characterised by bacterial invasion of the endothelial surface of the valves or the wall of the heart, resulting in fibrinous clots or vegetations that impede normal cardiac function. Although bacterial endocarditis can affect horses of all ages, it is predominantly found in animals less than 3 years of age (1).

Cases generally present for evaluation of fever of unknown origin. Clinical signs usually consist of fever with an audible heart murmur (grade 3/6 or louder) on either side of the thorax, with or without tachypnoea, tachycardia, cardiac arrhythmia or signs of congestive heart failure. Vegetative lesions are most commonly found on the mitral valve, followed by the aortic valve. Lesions on the tricuspid valve are less common and pulmonary valve lesions are rare.

Common bacterial isolates are Streptococcus spp., Actinobacillus spp.and Staphylococcus spp. (1, 2), but Serratia marcescens (3), Pseudomonas spp.and E. coli (4) have also been implicated. Cardiac arrhythmias may result from direct extension of the inflammatory lesion into the myocardium or may be secondary to thromboembolic myocardial ischaemia.

Key issues:

1. Fever and heart murmur are usually present.
2. Blood culture is important for diagnosis and to direct antimicrobial therapy.
3. Echocardiography is important to identify valve thickening, heart chamber size and degree of valvular regurgitation.

Diagnostics

Echocardiography can be used to detect thickening of the heart valves. Blood culture is indicated to identify bacteria present and direct antimicrobial therapy. Multiple blood cultures (5 collected at least 12 hours apart) may improve the likelihood of detecting a pathogen. Delaying therapy to allow adequate sample collection is recommended because the identity of the pathogens involved is unpredictable, as is their antibacterial susceptibility, and long durations of therapy are required.

Haematological analysis reveals leukocytosis, with a mature neutrophilia and elevated fibrinogen and Serum Amyloid A (SAA). An electrocardiogram is required if an arrhythmia is detected by auscultation, but this is rare.

Cardiac troponin I has been established as a sensitive and specific marker of myocardial injury (5). Although this is not always present, it could be useful for diagnosis and to monitor the response to treatment.

Treatment

Broad spectrum antimicrobial therapy is indicated until culture and susceptibility results are available. Resolution of clinical signs, decrease in the size of the lesion on echocardiographic examination and a reduction in leukocytosis, hyperfibrinogenaemia and SAA should determine the duration of therapy, which is likely to be several weeks.

Antimicrobials used

• Benzyl penicillin (22 000 IU/kg (12 mg/kg) IV q 6 h) and gentamicin (6.6 mg/kg IV q 24 h)
• Procaine penicillin G (22 000 IU/kg IM q 12 h) and gentamicin (6.6 mg/kg IV q 12 h)

Prognosis

Guarded to poor. Sterilisation of lesions can be difficult to achieve.

Marked chamber enlargement, severe deformation of the valve leaflets, severe valvular regurgitation and signs of congestive heart failure are grave prognostic indicators.

Purpura haemorrhagica

Purpura haemorrhagica (PH) is a non-septic, immune-mediated vasculitis that occurs as a rare complication of strangles (or vaccination against it), due to a type 3 hypersensitivity reaction. Typically, disease develops 2-4 weeks after infection with Streptococcus equi, although it may occur more quickly following vaccination (within a week). Although rare, vaccination with agents containing the SeM protein or avirulent S. equi are associated with an increased risk of PH. Occasionally PH may occur secondary to infection with another infectious organism. It appears to be caused by deposition of immune complexes on blood vessel walls following antigenic stimulation.

Painful pitting oedema results from a necrotising vasculitis. The head, limbs and trunk are most frequently affected with petechiation and ecchymoses of the mucous membranes. Severe oedema can result in exudation from the skin surfaces, and sloughing of the skin may occur. The vasculitis can affect other sites, including the gastrointestinal tract (resulting in colic), lungs (resulting in respiratory distress) and muscles (resulting in infarcts or muscle pain). Fever, tachycardia, tachypnoea, anorexia and depression are also frequently present. Renal dysfunction is common.

Secondary complications are common and can include laminitis and thrombophlebitis. Rarely, serious or even fatal haemorrhage can occur.

Diagnostics

In horses with evidence of PH, haematological and plasma biochemical analysis may reveal a leukopaenia or leukocytosis, anaemia, thrombocytopaenia, hyperfibrinogenaemia, hypo- or normoproteinaemia, and increased concentrations of muscle enzymes.

A presumptive diagnosis is generally made based on the history, clinical signs and exclusion of other causes of oedema. Elevated titres of IgA and IgG against S. equi are supportive of a diagnosis. Very high SeM-specific antibody titres (greater than 1:12,800) are strongly suggestive of PH secondary to strangles infection or vaccination. Skin biopsies can confirm leukocytoclastic vasculitis but are rarely performed.

Treatment

The objective of treatment is to reduce inflammation. Tapering doses of corticosteroids are used – typically dexamethasone, with initial dose of 0.1–0.2 mg/kg IM or IV for 3-5 days and then reducing the dose by half every 3-5 days over 2–4 weeks. Antimicrobials may be necessary where bacterial infection is concurrent or considered likely. Other supportive care such as hydrotherapy, supportive bandaging, IV fluids and non-steroidal anti-inflammatory drugs are usually required.

Antimicrobials used (include recommended dose rates/duration)

• None if uncomplicated
• If secondary infection is concurrent, broad-spectrum antimicrobials are indicated. Benzyl penicillin 22,000 IU/kg IV q 6 h and gentamicin 6.6 mg/kg q 24 h is a reasonable choice. Penicillin should not be used IM in these cases if muscle pain is present and care should be taken to ensure renal function is sufficient to tolerate gentamicin use. Trimethoprim/sulphadiazine (30 mg/kg IV or PO q 12 h) would be a reasonable alternative in cases where gentamicin is contraindicated, or IV penicillin is cost prohibitive.

Prognosis

The case fatality rate is ~10%. Relapse in clinical signs is common if corticosteroids are withdrawn too quickly. Anecdotally, treatment of relapsed disease is more difficult than treatment of horses in their first episode.

Vasculitis

Vasculitis can involve the arteries, veins or capillaries. Primary disease can occur because of direct damage to the vessel walls by an infectious agent, such as equine arteritis virus. This virus does occur in Australia, but disease associated with it has never been reported, suggesting that the virulence of Australian strains is low. Equine viral arteritis is a notifiable disease in Australia. More commonly in Australia, vasculitis occurs secondary to a bacterial or viral infection or endotoxaemia (14). Vasculitis secondary to infection with Streptococcus equi subsp equi is most common (see purpura haemorrhagica).

Vasculitis can also occur secondary to infection with equine herpesvirus 1 (EHV-1) (15)and, rarely, equine herpesvirus 4 (EHV-4), where there is also an immune-mediated pathogenesis. EHV-1 infection increases the procoagulant activity of peripheral blood mononuclear cell tissue factor (TF). The increase occurs during the acute infection and is most marked at the onset and end of viraemia. Tissue factor is an activator of the coagulation cascade during viral infection.

Key issues:

1. In Australia, vasculitis most commonly occurs secondary to bacterial or viral infections or endotoxaemia.
2. Clinical signs are painful-dependent-pitting oedema, sometimes with fever and petechial haemorrhages.

Diagnostics

Horses are usually febrile. The presence of painful, pitting oedema is consistent with the diagnosis. Haematological analysis is useful to determine white cell counts and neutrophil counts. When secondary to endotoxaemia, neutropaenia is common. When secondary to bacterial or viral infection, leucocytosis and neutrophilia are common.

Oedema due to low oncotic pressure should not be painful on palpation. In addition, normal serum albumin and protein, in association with a normal hydration status, rule out decreased oncotic pressure as cause of distal limb oedema.

Diagnosis of the primary disease should be attempted but may not be possible for viral aetiologies. Horses with endotoxaemic vasculitis are generally very unwell, with leukopaenia and neutropaenia. Plasma fibrinogen and SAA concentrations may be elevated during the initial stages, but this is dependent on the stage of disease. EHV-1 and EHV-4 can be diagnosed by isolation of virus from nasopharyngeal swabs or the buffy coat in blood samples collected into EDTA tubes, or by nucleic acid amplification (PCR testing). A rising serum antibody titre can also be used, but results are usually not known until after completion of the clinical course of disease.

Treatment

Anti-inflammatory therapy is indicated with flunixin meglumine at 0.25mg/kg IV q 8 h (anti-endotoxic dose) up to 1.1mg/kg q 12 h for full anti-inflammatory effect (0.5 mg/kg IV q 12 h is common).

Antimicrobial drugs are not indicated for treatment of vasculitis unless they may be required to treat the primary disease process (for example, procaine penicillin in the case of Streptococcus equi subsp equi infection – see purpura haemorrhagica; Section 2, Chapter 3).

Corticosteroids are indicated for treatment of immune-mediated diseases like purpura haemorrhagica (dexamethasone 0.1 – 0.2mg/kg IV q 24 h; prednisolone 0.10 - 0.2mg/kg PO q 24 h)

Antimicrobials used

• Not indicated for treatment of primary vasculitis.
• If secondary to Streptococcus equi subsp equi infection, then procaine penicillin G (22 000 IU/kg IM q 12 h, generally for 3-5 days) may be used concurrently with corticosteroids.

Prognosis

Can be guarded depending on the degree of vascular damage that occurs.