Infective endocarditis

Infective endocarditis (IE) is an infection of the endocardium, usually bacterial. It’s mostly a disorder of those with structural heart disease, but it can also occur in those with healthy hearts. It’s characterised by formation of vegetations on the heart valves. The most commonly affected valves are the aortic and mitral valves. IE is usually left-sided.

It’s usually a subacute disease, but it can develop acutely or chronically as well. The clinical features are variable, and so a high index of suspicion is needed. In many cases, correct diagnosis is delayed. It has high morbidity and mortality despite proper treatment. Neither the incidence nor the mortality have decreased in the past 30 years.

Etiology

Risk factors

• Artificial valves or other prosthetic material
• Damaged heart valves
• Congenital heart disease
• IV drug use
• Indwelling vascular catheters or pacemakers
• Dentistry procedures (only together with other risk factors)

Microbes:

• Acute IE – S. aureus
• Subacute IE – Streptococcus viridans, other streptococci
• Blood culture negative IE (BCNIE)
  • Brucella
  • Coxiella
  • Bartonella

In 5 – 10% of cases, blood cultures are negative (blood culture negative IE, BCNIE). This may be due to the causative pathogen not growing in normal blood cultures, or due to prior antibiotic therapy.

Rheumatic heart disease used to be a common cause but is now rare.

Pathology

Intact endothelium is resistant to bacteraemia, and so endothelial damage must be present for bacteria to colonize. Bacterial colonization results in:

• Destruction of the valve
• Embolisation of bacterial vegetations -> microemboli causing infarction in other organs
• Formation of immune complexes -> deposit in organs

IE can also lead to acute destruction of the valves leading to acute regurgitation or valve obstruction, possibly causing acute heart failure or cardiogenic shock.

Endocarditis almost always causes continous bacteraemia.

Embolisation

Embolisation occurs in 20-50% of cases of infective endocarditis, as parts of the vegetation loosens and travels elsewhere, causing infarction. These are so-called septic emboli. For left-sided endocarditis, embolisation occurs to the brain and spleen, while embolisation to the lungs is most common for right-sided endocarditis. Embolisation to vascular lumen or to the vasa vasorum causes characteristic aneurysms called mycotic aneurysms, which can rupture and cause bleeds. These most commonly occur intracerebrally. Septic embolisation of the kidney may cause acute kidney injury. Janeway lesions occur from septic emboli.

Immune complex formation

Immune complexes frequently form in infective endocarditis. These may cause glomerulonephritis, Osler nodes as well as Roth spots.

Classification

• According to affected side of heart
  • Left sided endocarditis
  • Right sided endocarditis – especially in IV drug users, unusual in others
• According to risk factors
  • Native valve infective endocarditis (NVIE)
  • Prosthetic valve endocarditis (PVE)
  • Endocarditis in association with implants (ICD and pacemaker)
  • Endocarditis in IV drug users (usually right sided)

Right sided endocarditis generally has a better prognosis than left-sided, but is much less common (5-10%).

Clinical features

Symptoms are variable, but in most cases the patient is visibly ill. Acute IE presents with marked toxicity and progresses over days or weeks. Subacute IE presents with only moderate toxicity and progresses over weeks to months. General symptoms include:

• Fever
• Shivering
• Night sweat
• Anorexia and weight loss
• Nausea and vomiting
• New or changed murmur

Embolism and deposition of immune complexes can cause the following phenomena (mostly in acute IE):

• Roth spots – retinal haemorrhages with pale middle
• Osler nodes – painful subcutaneous nodules on fingers, toes
• Janeway lesions – non-painful, erythematous macules on palms, soles
• Subuncal haemorrhage – Haemorrhages under fingernails
• Glomerulonephritis – due to deposition of immune complexes
• Neurological symptoms – stroke
  • Due to so-called “mycotic aneurysms” in the brain which rupture
  • Bacterial emboli embolize vasa vasorum of cerebral arteries, causing these aneurysms

Diagnosis and evaluation

Echocardiography and blood culture are essential in the evaluation of IE. Echocardiography may show the vegetations, but if nothing is visible on TTE, TEE should be performed. Blood culture must be taken in 3 separate sets with 30 minutes in-between, preferably before initiation of antibiotics.

In case of blood culture negative IE, PCR and serology may assist in detecting the pathogen. Inflammatory markers are elevated.

If echocardiography fails to show signs of valvular vegetations despite high likelihood of the diagnosis, PET-CT can be used to assess perivalvular infection.

Duke criteria

Diagnosis is based on the Duke criteria. There are major criteria and minor criteria, and the diagnosis is made when either of the following combinations are present:

• 2 major criteria + 0 minor criteria
• 1 major criteria + 3 minor criteria
• 0 major criteria + 5 minor criteria

These are the criteria:

• Major criteria
  • Blood cultures show typical organism
  • Echocardiographic evidence of endocarditis
  • New murmur
• Minor criteria
  • Predisposing risk factors (especially IV drug use)
  • Fever
  • Vascular abnormalities (emboli, intracerebral haemorrhage, etc.)
  • Immunological abnormalities (glomerulonephritis, Osler nodes, Roth spots, etc.)
  • Blood cultures show atypical organism

Treatment

Empirical intravenous antibiotic treatment is initiated after taking blood cultures, followed by specific antibiotics when results arrive. The specific empiric antibiotic regimen depends on local recommendations and the patient's risk factors (native or prosthetic valve, pacemaker/ICD, IV drug use, etc.). Antibiotic treatment for IE usually lasts 4 – 8 weeks, usually counted from the first day of definite improvement or from the day of the first negative blood culture. Penicillin/amoxicillin for streptococci, cloxacillin for staphylococci, depending on local resistance patterns.

Surgery is often necessary in IE, in as much as 50% of cases. Surgery is indicated for heart failure, uncontrolled infection, and in case of severe septic embolisation. Surgery is usually performed urgently. In case of cardiogenic shock, emergency surgery is indicated. If there is infected material (pacemaker/ICD leads), they should be removed.

Prophylaxis

Those at high risk (artificial valve, etc.) must practice good oral hygiene and avoid piercing and tattoos, etc. Before high-risk procedures like dental work or procedures involved infected tissues, these patients should take antibiotic prophylaxis.