Infective Endocarditis

The incidence of infective endocarditis is approximately 1.7-6.2 cases per 100,000 patient years, although rates are higher in at-risk cohorts such as intravenous drug users.¹ Incidence has remained constant for 50 years despite changes in the factors affecting incidence.²

Figures for incidence are similar between countries. It is 3 times more common in men and increasing in elderly patients (25-50% of cases occur in the over 60s) often associated with other disease, e.g. diabetes, cancer, alcoholism.

Risk factors

• Previous IE with valvular damage
• Invasive vascular procedures
• Recreational drug abuse
• Rheumatic heart disease (fewer than 20% of cases of IE)
• Elderly patients with calcific aortic stenosis
• Congenital heart disease accounts for 15% of cases (bicuspid aortic valve being the most common)
• Prosthetic valve implants

All cases have a nonbacterial thrombotic endocarditis (a sterile fibrin-platelet vegetation) as the prerequisite for adhesion and invasion. The site of this thrombus is influenced by the Venturi effect, with deposition of thrombus on the low pressure side.
There are differences in the different clinical situations:

• Acute IE:
  The thrombus may be produced either by the invading organism or by valvular trauma (pacing wires, catheters, etc.).
• Subacute IE:
  Sufficient inoculum of bacteria required to allow invasion of the thrombus, bacteria clumping with production of agglutinating antibodies.
• Nonbacterial thrombotic endocarditis:
  This can result from, for example, renal failure, neoplasia, systemic lupus erythematosus (SLE) or malnutrition.

The valves most commonly affected by infective endocarditis are (in decreasing order of frequency):

• Mitral valve
• Aortic valve
• Combined mitral and aortic valve
• Tricuspid valve
• Pulmonary valve - rare

• Early disease subtle and nonspecific
• Indolent process which may include:
  • Fatigue
  • Low-grade fever
  • Flu-like illness
  • Polymyalgia-like symptoms
  • Loss of appetite
  • Back pain
  • Pleuritic pain
  • Abdominal symptoms (may be pain, vomiting and appendicitis-like symptoms)
  • Symptoms akin to rheumatic fever
  • Weight loss
• Cerebrovascular accident - less common
• Congestive cardiac failure - less common
• May be history of:
  • Invasive procedures (see above)
  • Recreational drug use
  • Dental disease
  • Gingivitis - most cases caused by transient bacteraemia from this
  • Symptoms usually arise 2 weeks after invasive procedures but diagnosed after 6 weeks
  • Fewer than half of patients have previously-diagnosed valvular disease
• Developing disease produces a myriad of further clinical features of embolic or immunological origin when treatment/diagnosis delayed for weeks/months:
  • Acute meningitis - signs and symptoms but with sterile CSF
  • Hemiplegia from emboli in the middle cerebral artery (50% of patients may be first manifestation; has high mortality)
  • Renal infarcts causing painless haematuria
  • Splenic infarction causing pain
  • Blindness from retinal artery occlusion
  • Myocardial infarction from emboli in the coronary artery
  • Pulmonary emboli
  • Interstitial nephritis or proliferative glomerulonephritis from deposition of circulating immune complexes
  • Renal failure may result
  • Musculoskeletal symptoms (nearly half of patients) often from immunologically mediated synovitis
  • Immune-mediated vasculitis (causing Osler's nodes and Roth's spots)
  • Palpitations from immune-mediated myocarditis
  • Back pain (15% of patients) may have origin in immune complex deposition in disc spaces

Examination

• Fever: elderly, chronically ill patients with subacute IE may not have fever, but the majority do
• Heart murmurs:
  • Most patients have a murmur
  • Exception is right-sided IE where one third have murmurs
  • Only 15% have the classic 'changing murmur'
  • Most common murmur is aortic regurgitation
• Petechiae:
  • Conjunctivae
  • Hands and feet (dorsum)
  • Chest and abdominal wall
  • Oral mucosae and soft palate
• Splinter or subungual haemorrhages: Linear and red
• Osler's nodes: small tender red-to-purple nodules pulp of terminal phalanges fingers and toes
• Clubbing: only 10% of cases and usually in longstanding subacute IE
• Roth's spots: retinal haemorrhages with pale centres
• Janeway's lesions: irregular painless erythematous macules on the thenar and hypothenar eminence (usually with acute IE and S. aureus)
• Arthritis:
  • With subacute IE usually asymmetric and up to 3 joints affected (fluid sterile)
  • Acute IE can give acute septic monoarticular arthritis
• Splenomegaly: most often observed in longstanding subacute disease and often persists after treatment
• Meningism/meningitis: purulent disease occurs in acute IE and aseptic variety in subacute IE

The differential diagnosis could include all those conditions which occur as a complication or with progression of the disease.

Some of the more unusual diseases which may also have similar complex and varied manifestations are:

• SLE
• Atrial myxoma and other cardiac neoplasms
• Lyme disease
• Antiphospholipid syndrome
• Polymyalgia rheumatica
• Reactive arthritis

Blood cultures

• Blood cultures are used to demonstrate bacteraemia of 30 minutes or more duration
• Draw 3 to 5 sets of blood cultures over 24 hours
• In acute IE, 3 sets drawn from different venepuncture sites over 30 minutes demonstrates continuous bacteraemia
• If cultures are negative 24 hours after stopping antibiotics, repeat after 7 days and, if still negative, reconsider IE diagnosis
• Blood should not be drawn from IV lines (unless diagnosing line infection when simultaneous line and peripheral vein sampling may be used)
• Prior use of antibiotics commonly gives false negative results
• Probably 50% of culture results are estimated to be falsely positive
• Fastidious organisms may require special culture media or prolonged incubation
• HACEK organisms may require 3 weeks of culture and brucella organisms up to 6 weeks

Serological tests

These may be necessary to detect some organisms, e.g. legionella, chlamydia, brucella and coxiella species.

Imaging studies

Echocardiography is the indirect investigative method of choice. Note in general terms that:

• Echocardiography is particularly useful in the elderly
• Echocardiography is especially of use when clinical picture of IE but negative cultures
• Echocardiography is useful to predict complications such as embolisation:
  • Larger vegetations (>10 mm diameter)
  • Multiple vegetations
  • Pedunculated vegetations
  • Prolapsing vegetations
• Diagnosis of IE can never be excluded with negative echocardiogram (of whatever type)
• Echocardiography should not be used to screen for IE because of high (15% plus) false positive rate (caused by thickened valves, etc.)

Transthoracic echocardiography (TTE):

• TTE is the initial technique of choice for investigating infective endocarditis.¹
• Can detect vegetations in 60% of native valve endocarditis but much less often in prosthetic valves
• TTE is good enough for most cases of IE

Transoesophageal echocardiography (TEE):

• In high risk groups, TEE, with its higher sensitivity and specificity, may be needed if the TTE is normal and suspicion of infective endocarditis remains high¹
• Was developed to visualise prosthetic valves and right-sided pathology
• It detects over 90% of all vegetations
• TEE is better at detecting myocardial abscesses and vegetations on pacemaker leads

Two dimensional cardiac ultrasound Doppler studies have been a helpful advance providing more information on vegetations:

• This may help in diagnosis but also in predicting risk of embolisation
• Useful for visualising jet lesions and cusp perforation

Radionucleotide studies are of little value except for detecting splenic abscesses which are refractory to antibiotic treatment.
Electrocardiogram is useful to detect the 10% of patients who will develop conduction defects.

Diagnostic criteria

Have a high index of suspicion:

• Admit the patient to hospital for full investigation:
  • Blood cultures
  • Temperature records
  • Basic haematology and biochemistry investigations
  • ECG and CXR
  • Comprehensive TTE
• Blood cultures:
  • With a sick patient (acute IE) take 3 sets of cultures at >1 hour intervals.
  • Less obvious IE (sub-acute presentation) requires 6 sets of cultures over 24-48 hours.
  • Cultures negative for the commoner organisms should be checked for unusual slow-growing organisms and fungi.
• Referral:
  • When blood cultures are positive to a cardiologist.
  • At the outset to a microbiologist.
• TTE or TEE:
  • If TTE difficult or suboptimal.
  • In order further to assess vegetations, abscesses or valvular perforations.
  • In all patients with prosthetic valve endocarditis (PVE).
• Serological testing:
  • If the diagnosis is still suspected but cultures negative after 7 days.
  • Tests for Coxiella burnetii, Bartonella spp. and chlamydial organisms are available and should be performed.
• Testing of biopsied tissue with special techniques to identify bacteria and fungi are being developed.

Guidelines have been produced for treating IE.^4,5,6

Surgery is needed in approximately 50% of patients who develop infective endocarditis and careful timing is essential to ensure a good outcome:¹

• In most stable patients surgery is best delayed until antibiotics are completed to reduce the risk of perioperative complications and early prosthetic valve endocarditis.
• Unstable patients with haemodynamic or perivalvular complications have a poor prognosis and are best transferred to a specialist centre at the earliest opportunity.

These are an inherent part of the progression of the disease. Patients should be monitored for:

• Valve dysfunction
• Myocardial abscesses
• Embolic phenomena
• Heart failure
• Metastatic infection
• Immunological disease and organ dysfunction
• Complications even after bacteriological cure
• Conduction defects (patients with IE should have daily ECGs)

This varies markedly according to a variety of factors. The following outlines the range of prognosis when managed appropriately:

• Native valve endocarditis:
  • S. viridans 98% cure rate
  • S. aureus 60-90% cure rate with worse results in occurring in those NOT abusing intravenous drugs
  • Fungal infections - cure rate less than 50%
• PVE:
  • Cure rates at least 10% lower than above for each variety
  • Surgery needed more often

See Prevention of Endocarditis record for details.