Endocarditis is characterized by a prototypic lesion, the vegetation, which is a mass of platelets, ﬁbrin, microcolonies of microorganisms, and scant inﬂammatory cells. In the subacute form of infective endocarditis, the vegegation may also include a center of granulomatous tissue, which may fibrose or calcify.
There are multiple ways to classify endocarditis. The simplest is classifying based on etiology: either infective or non-infective, depending on whether a microorganism is the source of the inflammation. Regardless, diagnosis of this disease is based on the clinical features, investigations such as echocardiogram, as well as any blood cultures exhibiting the existence of microorganisms commonly causing endocarditis.
As the valves of the heart do not actually receive any supply of their own, defensive immune mechanisms (such as white blood cells) cannot approach the valves. So if an organism (such as bacteria) establishes a hold on the valves forming a vegetation, the body cannot get rid of them. Also, the lack of blood supply to the valves has implications on treatment, since drugs also have difficulty reaching the infected valve.
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.
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 can be 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, or due to absence of an organism as in marantic endocarditis. Some pathogens responsible for culture-negative endocarditis include Aspergillus species, Brucella species, Coxiella burnetii, Chlamydia species, and HACEK bacteria.
Patients who inject narcotics intravenously may introduce infection which will travel to the right side of the heart classically affecting the tricuspid valve, and most often caused by Staphylococcus aureus. In other patients without a history of intravenous exposure, endocarditis is more frequently left-sided.
Another form of endocarditis is nosocomial endocarditis which is when the patient is diagnosed with endocarditis and has had hospital care one month prior to the incident and is usually secondary to IV catheters, TPN lines, pacemakers, etc.
Finally, the distinction between native-valve endocarditis and prosthetic-valve endocarditis is clinically important. Prosthetic valve endocarditis can be early (< 2 months of valvular surgery) or late (> 2 months of valvular surgery). Early prosthetic valve endocarditis is usually due to intraoperative contamination or a postoperative bacterial contamination which is usually nosocomial in nature. Late prosthetic valve endocarditis is usually due to community acquired microorganisms.
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, although this practice has changed in the US with new American Heart Association guidelines released in 2007 (Circulation 2007 Oct 9;116(15):1736-54) and in the UK as of March 2008 due to new NICE guidelines.
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.)
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.
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]
Chest X-Ray (Pulmonary Embolism at Right sided failure)
Evidence of endocardial involvement Positive echocardiogram for IE defined as :
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.
In acute endocarditis, due to the fulminant inflammation empirical antibiotic therapy is started immediately after the blood has been drawn for culture. This usually includes oxacillin and gentamicin IV infusions until the culture sensitivity report with the minimum inhibitory concentration comes, when the therapy can be modified to tailor to the microorganism.
In subacute endocarditis, antibiotic treatment is based on the microorganism involved, requiring the culture sensitivity report. So immediate therapy is mainly focused on symptomatic treatment.
The most common organism responsible for 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. Again it is important to note that antibiotic therapy hinges upon the culture sensitivity report.
Another regimen that is followed for endocarditis is the short course treatment which is a 2 week treatment regimen of benzyl penicillin IV which may be sufficient for Streptococcus viridans and Streptococcus bovis so long as the following conditions are met:
‣ Endocarditis of a native valve, not on a prosthetic valve
‣ An MIC ≤ 0.1 mg/l
‣ No evidence of thromboembolism
‣ No vegetations > 5mm in diameter
‣ Clinical response within 7 days
The short course treatment In patients where the blood culture reveals the causative organism, culture sensitivity reports should be followed to treat the patient, in addition to usage of two bactericidal antibiotics for a minimum of two weeks as a combination therapy.
Surgical debridement of infected material and replacement 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. Other indications to consider surgery include:
‣ Unstable Prosthetic Valve or Obstruction
‣ Recurrent septic emboli, mycotic aneurysm
‣ Large vegetations
‣ Abscess formation
‣ Early closure of mitral valve
‣ Gram negative species
Infective endocarditis is associated with a 25% mortality.
Typically NBTE does not cause many problems on its own, but parts of the vegetations may break off and embolize to the heart or brain, or they may serve as a focus where bacteria can lodge, thus causing infective endocarditis.
Another form of sterile endocarditis, which is fairly rare, is termed Libman-Sacks endocarditis; this form occurs more often in patients with lupus erythematosus and is though to be due to the deposition of immune complexes. Like NBTE, Libman-Sacks endocarditis involves small vegetations, while infective endocarditis is composed of large vegetations. These immune complexes precipitate an inflammation reaction, which helps to differentiate it from NBTE. Also unlike NBTE, Libman-Sacks endocarditis does not seem to have a preferred location of deposition and may form on the undersurfaces of the valves or even on the endocardium.