Endocarditis

Endocarditis
Specialty	Cardiology, infectious disease

Endocarditis is an inflammation of the inner layer of the heart, the endocardium. The most common structures involved are the heart valves.

Endocarditis can be classified by etiology as either infective or non-infective, depending on whether a microorganism is the source of the problem.

Infective endocarditis

As the valves of the heart do not actually receive any blood supply of their own, defense mechanisms (such as white blood cells) cannot enter. So if an organism (such as bacteria) establishes a hold on the valves, the body cannot get rid of them.

Normally, blood flows smoothly through these valves. If they have been damaged (for instance in rheumatic fever) bacteria can have a chance to take hold.

Classification

Traditionally, infective endocarditis has been clinically divided into acute and subacute (because the patients tend to live longer in subacute as opposed to acute) endocarditis. This classifies both the rate of progression and severity of disease. Thus subacute bacterial endocarditis (SBE) is often due to streptococci of low virulence and mild to moderate illness which progresses slowly over weeks and months and has low propensity to hematogenously seed extracardiac sites, while acute bacterial endocarditis (ABE) is a fulminant illness over days to weeks, and is more likely due to Staphylococcus aureus which has much greater virulence, or disease-producing capacity and frequently causes metastatic infection.

This terminology is now discouraged. The terms short incubation (meaning less than about six weeks), and long incubation (greater than about six weeks) are preferred.

Infective endocarditis may also be classified as culture-positive or culture-negative. Culture-negative endocarditis is due to micro-organisms that require a longer period of time to be identified in the laboratory. Such organisms are said to be 'fastidious' because they have demanding growth requirements. Some pathogens responsible for culture-negative endocarditis include Aspergillus species, Brucella species, Coxiella burnetii, Chlamydia species, and HACEK bacteria.

Finally, the distinction between native-valve endocarditis and prosthetic-valve endocarditis is clinically important.

Patients who inject narcotics intravenously may introduce infection which will travel to the right side of the heart, most often staphylococcus aureus. In other patients without a history of intravenous exposure, endocarditis is more frequently left-sided.

Etiology and pathogenesis

As previously mentioned, altered blood flow around the valves is a risk factor in obtaining endocarditis. The valves may be damaged congenitally, from surgery, by auto-immune mechanisms, or simply as a consequence of old age. The damaged part of a heart valve becomes covered with a blood clot, a condition known as non-bacterial thrombotic endocarditis (NBTE).

In a healthy individual, a bacteremia (where bacteria get into the blood stream through a minor cut or wound) would normally be cleared quickly with no adverse consequences. If a heart valve is damaged and covered with a piece of a blood clot, the valve provides a place for the bacteria to attach themselves and an infection can be established.

The bacteremia is often caused by dental procedures (in most cases due to viridans streptococci, which reside in oral cavity), such as a cleaning or extraction of a tooth. It is important that a dentist or a dental hygienist is told of any heart problems before commencing. Antibiotics are administered to patients with certain heart conditions as a precaution.

Another group of causes result from a high number of bacteria getting into the bloodstream. Colorectal cancer (mostly Streptococcus bovis), serious urinary tract infections (mostly enterococci), and IV drug (Staphylococcus aureus) use can all introduce large numbers of bacteria. With a large number of bacteria, even a normal heart valve may be infected. A more virulent organism (such as Staphylococcus aureus, but see below for others) is usually responsible for infecting a normal valve.

Intravenous drug users tend to get their right heart valves infected because the veins that are injected enter the right side of the heart. The injured valve is most commonly affected when there is a pre-existing disease. (In rheumatic heart disease this is the aortic and the mitral valves, on the left side of the heart.)

Clinical and pathological features

• Fever, i.e. fever of unknown origin (often spiking caused by septic emboli)
• Continuous presence of micro-organisms in the bloodstream determined by serial collection of blood cultures
• Vegetations on valves on echocardiography, which sometimes can cause a new or changing heart murmur, particularly murmurs suggestive of valvular regurgitation
• Vascular phenomena: Septic emboli (causing thromboembolic problems such as stroke in the parietal lobe of the brain or gangrene of fingers), Janeway lesions (painless hemorrhagic cutaneous lesions on the palms and soles), intracranial hemorrhage, conjunctival hemorrhage, splinter hemorrhages
• Immunologic phenomena: Glomerulonephritis, Osler's nodes (painful subcutaneous lesions in the distal fingers), Roth's spots on the retina, positive serum rheumatoid factor

Diagnosis

The most important investigation is Blood culture. In general, a patient should fulfill the Duke Criteria in order to establish the diagnosis of endocarditis.

As the Duke Criteria relies heavily on the results of echocardiography, research has addressed when to order an echocardiogram by using signs and symptoms to predict occult endocarditis among patients with intravenous drug abuse and among non drug-abusing patients . Unfortunately, this research is over 20 years old and it is possible that changes in the epidemiology of endocarditis and bacteria such as staphylococcus make the following estimates incorrectly low.

Among patients who do not use illicit drugs and have a fever in the emergency room, there is a less than 5% chance of occult endocarditis. Mellors in 1987 found no cases of endocarditis nor of staphylococcal bacteremia among 135 febrile patients in the emergency room. The upper confidence interval for 0% of 135 is 5%, so for statistical reasons alone, there is up to a 5% chance of endocarditis among these patients. In contrast, Leibovici found that among 113 non-selected adults admitted to the hospital because of fever there were two cases (1.8% with 95%CI: 0% to 7%) of endocarditis.

Among patients who do use illicit drugs and have a fever in the emergency room, there is about a 10% to 15% prevalence of endocarditis. This estimate is not substantially changed by whether the doctor believes the patient has a trivial explanation for their fever. Weisse found that 13% of 121 patients had endocarditis. Marantz also found a prevalence of endocarditis of 13% among such patients in the emergency room with fever. Samet found a 6% incidence among 283 such patients, but after excluding patients with initially apparent major illness to explain the fever (including 11 cases of manifest endocarditis), there was a 7% prevalence of endocarditis.

Among patients with staphylococcal bacteremia (SAB), one study found a 29% prevalence of endocarditis in community-acquired SAB versus 5% in nosocomial SAB. However, only 2% of strains were resistant to methicillin and so these numbers may be low in areas of higher resistance.

Echocardiography
The transthoracic echocardiogram has a sensitivity and specificity of approximately 65% and 95% if the echocardiographer believes there is 'probabable' or 'almost certain' evidence of endocarditis.

[Discussion is needed here, including transthoracic versus transesophageal]

Blood Cultures:-

• >3 Blood samples from 3 different venepuncture sites

ECGs (MI)

Chest X-Ray (Pulmonary Embolism at Right sided failure)

Duke's Criteria

Major Criteria

Positive blood culture for Infective Endocarditis Typical microorganism consistent with IE from 2 separate blood cultures, as noted below:

• viridans streptococci, Streptococcus bovis, or HACEK group, or
• community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus or Microorganisms consistent with IE from persistently positive blood cultures defined as:

• 2 positive cultures of blood samples drawn >12 hours apart, or
• all of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 hour apart)

Evidence of endocardial involvement Positive echocardiogram for IE defined as :

• oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation, or
• abscess, or
• new partial dehiscence of prosthetic valve or New valvular regurgitation (worsening or changing of preexisting murmur not sufficient)

Minor Criteria

• Predisposing factor presence
• Fever >38 degree Celsius
• Immunological problems like Glomerulonephritis, Osler's Nodes
• Positive Blood Culture
• Evidence of embolism
• Positive Echocardiogram

Micro-organisms responsible

Many types of organism can cause infective endocarditis. These are generally isolated by blood culture, where the patient's blood is removed, and any growth is noted and identified.

Alpha-haemolytic streptococci, that are present in the mouth will often be the organism isolated if a dental procedure caused the bacteraemia.

If the bacteraemia was introduced through the skin, such as contamination in surgery, during catheterisation, or in an IV drug user, Staphylococcus aureus is common.

A third important cause of endocarditis is Enterococci. These bacteria enter the bloodstream as a consequence of abnormalities in the gastrointestinal or urinary tracts. Enterococci are increasingly recognized as causes of nosocomial or hospital-acquired endocarditis. This contrasts with alpha-haemolytic streptococci and Staphylococcus aureus which are causes of community-acquired endocarditis.

Some organisms, when isolated, give valuable clues to the cause, as they tend to be specific.

• Candida albicans, a yeast, is associated with IV drug users and the immunocompromised.
• Pseudomonas species, which are very resilient organisms that thrive in water, may contaminate street drugs that have been contaminated with drinking water. P. aeruginosa can infect a child through foot punctures, and can cause both endocarditis and septic arthritis.
• Streptococcus bovis and Clostridium septicum, which are part of the natural flora of the bowel, are associated with colonic malignancies. When they present as the causative agent in endocarditis, it usually call for a concomitant colonoscopy due to worries regarding hematogenous spread of bacteria from the colon due to the neoplasm breaking down the barrier between the gut lumen and the blood vessels which drain the bowel.
• HACEK organisms are a group of bacteria that live on the dental gums, and can be seen with IV drug abusers who contaminate their needles with saliva. Patients may also have a history of poor dental hygiene, or pre-existing valvular disease.

Treatment

High dose antibiotics are administered by the intravenous route to maximize diffusion of antibiotic molecules into vegetation(s) from the blood filling the chambers of the heart. This is necessary because neither the heart valves nor the vegetations adherent to them are supplied by blood vessels. Antibiotics are continued for a long time, typically two to six weeks. Specific drug regimens differ depending on the classification of the endocarditis as acute or subacute (acute necessitating treating for Staphylococcus aureus with oxacillin or vancomycin in addition to gram-negative coverage). Fungal endocarditis requires specific anti-fungal treatment, such as amphotericin B. The most common organism responsible for the majority of Infective Endocarditis is Streptococcus viridans, which is highly sensitive to Penicillin. High dose IV Crystalline Penicillin 20L every 4hrs for 2 weeks is recommended and still remains the drug of choice. In pts where Blood culture reveals the causative organism, a combination of therapy with two bactericidal antibiotics for at least 2 weeks is a must.

Surgical removal of the valve is necessary in patients who fail to clear micro-organisms from their blood in response to antibiotic therapy, or in patients who develop cardiac failure resulting from destruction of a valve by infection. A removed valve is usually replaced with an artificial valve which may either be mechanical (metallic) or obtained from an animal such as a pig; the latter are termed bioprosthetic valves.

Infective endocarditis is associated with a 25% mortality.

Non-infective endocarditis

Non-infective or marantic endocarditis is rare. A form of sterile endocarditis is termed Libman-Sacks endocarditis; this form occurs more often in patients with lupus erythematosus and the antiphospholipid syndrome. Non-infective endocarditis may also occur in patients with cancers, particularly mucinous adenocarcinoma.

External links

• Endocarditis information from Seattle Children's Hospital Heart Center