Chapter 17 Fever
Endocarditis and pericarditis
Infective endocarditis is a microbial infection of the endothelial surface of the heart. In horses, infective endocarditis is characterized by bacterial or fungal invasion of the valves (valvular endocarditis) or wall of the endocardium (mural endocarditis) resulting in fibrinous clots or vegetations. Although infective endocarditis affects horses of all ages, the median age is 5 years with a range of reported cases from 2 months to 15 years.1–20 Males are more likely to be affected than females. No breed predilection has been found.
Infective endocarditis predominantly affects the left side of the heart in the horse. The prognosis is poor in these cases because even with bacteriological cure, persistent regurgitation often leads to left ventricular volume overload, left heart failure and pulmonary hypertension.
The most frequently seen clinical signs are intermittent or continuous fever, cardiac murmur, tachycardia and tachypnoea.1–20 Shifting leg lameness, intermittent joint distention, coughing, ventral oedema and depression are less commonly seen. Fever is present in almost all cases of infective endocarditis1–22 and in many cases is the primary complaint.5 Shifting leg lameness may be associated with effusion of one or more synovial structures. The lameness may be due to haematogenous synovial sepsis, emboli or immune complex deposition. Signs of congestive heart failure may be present in severely affected individuals. Clinical signs of left heart failure in the horse include tachypnoea, crackles and harsh lung sounds on thoracic auscultation. Signs of right heart failure are ventral oedema, venous distention and jugular vein pulsation.
The mitral valve is most often affected in the horse followed by the aortic, tricuspid and then the pulmonary valve.5,18 The predominance of mitral valve endocarditis is also reported in some other species.26 Cardiac murmurs associated with infective endocarditis in the horse are generally harsh holosystolic band-shaped grade 3/6 or louder if the atrioventricular valves are involved. If the semilunar valves are affected, the murmur is most often decrescendo holodiastolic grade 2/6 or louder. Cardiac murmurs are most often associated with regurgitation through the affected valve although murmurs of valvular stenosis can occur.11 All horses with aortic or mitral valve involvement had a cardiac murmur.1–3,6–20 Right-sided vegetative lesions may not produce a cardiac murmur as a result of a lower pressure difference between the right atrium and ventricle in comparison to left-sided pressures.3–5 Mural and small valvular lesions also may not produce a cardiac murmur. If a cardiac murmur is not present and bacterial endocarditis is suspected, an echocardiogram should be performed to examine the valves for vegetative lesions.
Cardiac dysrhythmias in horses with bacterial endocarditis, although uncommon, may occur as a result of direct extension of the inflammatory lesion into the myocardium or thromboembolic myocardial ischaemia. Cardiac dysrhythmias reported in horses with bacterial endocarditis include atrial fibrillation, ventricular tachycardia and supraventricular and ventricular extrasystoles.5,12,14,17,18
The source of infection is often not determined in the horse. Infective endocarditis has been associated with jugular vein thrombophlebitis5,21,22 and with the presence of a transvenous pacing catheter23 in the horse. Congenital heart disease is a frequent finding in human beings with infective endocarditis24 but has not been reported in the horse. Many species of bacteria cause infective endocarditis in the horse. Streptococcus spp. and Actinobacillus spp. are the most common organisms cultured from horses with infective endocarditis although a wide range of pathogens has been reported.1–20 Two reports of infective endocarditis were attributed to fungal infection with Aspergillus and Candida species.7,18 Borrelia burgdorferi has also been implicated.25
Bacteraemia allows bacteria to reach the heart by haematogenous spread through blood in the chambers of the heart. Breaks in the endothelial surface may occur in three ways: (1) high-velocity jet impacting the endothelium; (2) flow from high to low pressure chamber; and (3) flow across a narrow orifice at high velocity.24 The organism invades the valve through breaks in the endothelial surface. If the endothelium on the valve surface is damaged, platelets and fibrin are deposited. The platelet–fibrin complex is more receptive to bacterial colonization than intact endothelium and shields the bacteria from phagocytosis. Papilliferous masses of platelets, fibrin and bacteria supported by a bed of granulation tissue develop on the valve surface and are known as vegetations. Vegetations are found at the valve-closure line in the atrial surface of the atrioventricular valves and on the ventricular surface of the semilunar valves.
The clinical signs of infective endocarditis result from: (1) local destructive effects of intracardiac infection; (2) embolization of fragments of the vegetations to distant sites resulting in infection or infarction; (3) haematogenous seeding of remote sites during continuous bacteraemia and metastatic infection; and (4) deposition of immune complexes in tissues resulting in synovitis and glomerulonephritis.24 The vegetations distort the valvular architecture, which leads to valvular incompetence and/or stenosis and cardiac murmur. If regurgitation through the affected valve is sufficient, congestive heart failure can develop. In addition, local destruction of tissues may lead to chordae tendineae rupture and perforation or fistulas between cardiac chambers or major blood vessels. Myocardial infection and myocardial microabscess may cause disruption of the conduction system, dysrhythmias and myocardial failure. Arterial emboli originating from the vegetation most commonly affect the coronary arteries, kidney, spleen, brain and lung, resulting in specific clinical signs.24
The haemodynamic consequences of infective endocarditis are dependent on the valve(s) affected, degree of regurgitation and severity of the infection. In cases of mitral valvular lesions and significant regurgitation, the excessive pressure in the left atrium may be transferred retrograde to the pulmonary vasculature and pulmonary oedema may develop. The high pressures may also be transferred to the pulmonary artery and right heart resulting in signs of right heart failure with the potential for pulmonary artery rupture. In general, aortic regurgitation is better tolerated in the horse. Moderate to severe aortic regurgitation may cause left ventricular volume overload, dilation and subsequent mitral regurgitation. Tricuspid regurgitation is less likely to have significant haemodynamic effects but the potential for right heart failure exists.
Hyperfibrinogenaemia, leucocytosis with a mature neutrophilia, hyperproteinaemia and anaemia are the most common abnormal laboratory findings in horses with infective endocarditis.1–19 Hyperproteinaemia reflects hypergammaglobulinaemia. The anaemia is nonregenerative and is typical of anaemia of chronic disease. Thrombocytopaenia occurs uncommonly. Prerenal azotaemia may accompany dehydration or shock. Azotaemia may also be found in patients with bacterial endocarditis if congestive heart failure, immune mediated glomerulonephritis or renal infarcts or emboli are present. Serum amyloid A and cardiac troponin I may also be useful in diagnosis and monitoring of treatment.
Bacteraemia associated with bacterial endocarditis is continuous but the number of bacteria at any one time may fluctuate.27 Ideally, three blood cultures should be obtained at least 1 hour apart prior to the initiation of antimicrobial therapy. Blood should be cultured in aerobic and anaerobic media for at least 4 days before determining that the culture is negative. Obtaining blood for cultures during peak temperature elevation has not been shown to increase the number of positive cultures.24 Previous antimicrobial administration has been shown to inhibit positive blood culture for 7–10 days in human beings.24 Therefore, withholding antimicrobials to improve the success rate of a positive blood culture is not warranted in the acute case. Antimicrobial removal devices have been shown to be effective in increasing the likelihood of a positive blood culture in patients that are receiving antimicrobials.28 Negative blood cultures should not rule out bacterial endocarditis especially in horses previously treated with antimicrobials.
Echocardiography provides an accurate diagnosis by identifying the location of the lesion(s) and determining its size. It should be performed in all patients suspected of infective endocarditis regardless of a negative blood culture. Echocardiography is also useful in formulating a prognosis by assessing degree of chamber enlargement, severity of regurgitation and extent of myocardial dysfunction. In humans transoesophageal echocardiography using biplane technology is the preferred approach. Due to size and financial limitations, this technology is not used in clinical practice in the horse. Vegetative lesions on the valves, chordae tendineae, mural endocardium or intimal surface of the great vessels appear as irregular shaggy hypoechoic to echogenic masses on the echocardiogram. Vegetative lesions that extend from the valve margins can result in a flailing motion with movement of the affected valve leaflet. The shaggy thickened appearance of the valve may also be detected on M-mode echocardiography. Ruptured chordae tendineae associated with vegetative lesions may also be detected with echocardiography as a flail valve leaflet. Extension of the infection beyond the valve leaflet worsens the prognosis. In less severe cases, the lesion may appear as an irregular thickening. These lesions may be difficult to distinguish from severe degenerative valvular disease. Clinical signs, clinical pathology data, age of the animal and response to therapy must all be taken into account in these cases. Appropriate antimicrobial therapy should be initiated until an alternative diagnosis is reached. ( RCT)
Doppler interrogation of the affected valve should be performed to semiquantitate the severity of regurgitation or stenosis and spectral and colour flow Doppler are used to map the size and location of the regurgitant jet29–33 (see Chapter 9). In significant mitral regurgitation, left atrial and ventricular enlargement are present.33 The severity of the enlargement is dependent on the amount and duration of the regurgitation and may be relatively mild in the early stages of the disease even in the presence of severe regurgitation. Rounding of the left ventricular apex suggests left ventricular volume overload. The left parasternal 2-chamber view of the left atrium provides the best image to measure left atrial diameter.29,33 Increases in left atrial pressures create a turgid round appearance of the left atrium and bulging of the interatrial septum to the right.33
Dilation of the pulmonary artery is an indicator of pulmonary hypertension.33 The pulmonary artery diameter obtained in the two-dimensional right parasternal view of the right outflow tract should be less than or equal to the aortic diameter obtained in the right parasternal left outflow tract view.33 If the pulmonary artery diameter exceeds the aortic diameter, pulmonary hypertension is present. Horses with pulmonary hypertension are at risk for sudden death secondary to rupture of the pulmonary artery.33 A smaller than normal aortic diameter is compatible with low left ventricular output and left heart failure.33
Moderate to severe aortic regurgitation results in left ventricular volume overload34 and in left ventricular dilation the interventricular septum and left ventricular free wall may become thin.29,34 Fractional shortening is expected to be above normal in horses with volume overload and concurrent normal myocardial function. A normal or decreased fractional shortening is indicative of myocardial dysfunction.29,34 The aortic root becomes dilated in moderate to severe aortic regurgitation most likely because of increased blood flow into the aorta.29,34 Premature closure of the mitral valve may occur in cases of severe regurgitation due to the volume overload.35 In addition, the septal leaflet of the mitral valve may have high-frequency diastolic flutter visible on M-mode echocardiography.29,34,35
Doppler echocardiography of the aortic valve can be performed from the right parasternal long-axis view of the left outflow tract, the right parasternal short-axis view of the aorta or the left parasternal long-axis view of the left outflow tract. The most parallel flow signal is from the left parasternal window.29 Aortic regurgitation jets are either directed towards the left apex or travel laterally towards the left ventricular free wall.32 A sharp decline (steep slope) in the continuous wave Doppler spectral tracing of the aortic regurgitation indicates a rapid increase in left ventricular diastolic pressure and severe aortic regurgitation.32 The severity of regurgitation is determined by the distance the regurgitant jet travels into the left ventricular outflow tract and the width of the jet at its origin.32 A regurgitant jet that extends into more than two-thirds of the left ventricular outflow tract beyond the septal leaflet of the mitral valve is considered severe.32
When tricuspid regurgitation is moderate to severe, right atrial enlargement will be present.35 Volume overload of the right ventricle will present with right ventricle enlargement and possible dilation.29 Paradoxical septal motion occurs when there is severe tricuspid regurgitation and right ventricular volume overload.35 A regurgitant jet that occupies more than two-thirds of the atrium is considered severe.29
Serial echocardiography can be used to assess therapeutic success. A decrease in lesion size, increase in echogenicity of the lesion and smoothing of the vegetative lesion is consistent with resolution of the infection as a result of fibrous scar tissue formation and contracture. However, studies in human beings indicate that infective endocarditis that is ultimately successfully treated with antimicrobial therapy may not show any change in the appearance of the lesions.24 Changes in vegetations must be interpreted in a clinical context and do not in themselves reflect the efficacy of therapy.24