Endocarditis: Pathology review

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Case Study0:00–0:39

Two people came into the cardiology ward. One of them was 25 year old Darren, who came in with a fever, chills and fatigue.
On the clinical examination, his fingernails had splinter hemorrhages and the palm of his hands had some erythematous flat lesions.
There were also some track marks on his forearm. The other one is 75 year old Anna, who also had a fever and the same splinter hemorrhages and erythematous flat lesions that we previously saw.
On auscultation, a heart murmur was heard. On her history, she said she was at the dentist 2 weeks ago.
Okay, so both people likely have endocarditis, or inflammation of the inner layer of the heart. Remember that the heart’s wall is made up of three layers, the epicardium being the outermost layer, then the myocardium, and the endocardium, which is the layer that gets inflamed.

Pathology0:39–1:17

The inflammation can affect the heart valves, the mural endocardium or even prosthetic valves! The most common cases of endocarditis are due to a microbial infection, and this is called infective endocarditis but in some cases, endocarditis can also be non-infective.

Non-Infect. Endocarditis1:17–2:35

For non-infective endocarditis, the first step is usually damage to the endocardium. Damage exposes the underlying collagen and tissue factor, which causes platelets and fibrin to adhere, which forms tiny blood clots.
This is called Nonbacterial Thrombotic Endocarditis or NBTE. Tiny clots and fibrin can develop into vegetation, especially on the heart valves which damages them and makes it harder for them to open or close.
Although the exact cause of NBTE is unknown, it’s thought that a proinflammatory state where cytokines levels are elevated can increase clot formation.
This can happen with hypercoagulable states, like when there’s a malignancy, especially pancreatic adenocarcinoma. Another situation where NBTE can happen is with systemic lupus erythematosus, This is an autoimmune disease involving antigen-antibody complexes, and in this case they settle in the endocardium and cause inflammation, leading to a particular type of endocarditis, called Libman-Sacks endocarditis.
Remember that it’s associated with large vegetations, sometimes described as verrucous vegetations since they look like warts.
Now, infective endocarditis occurs when pathogens find their way to the endocardium, typically from the heart valves. Every day, there are opportunities for pathogens like bacteria and fungi to get into the bloodstream, but this is not a problem because they are usually few in number and can easily be cleared by our immune system.

Infective Endocarditis2:35–3:50

However, sometimes a larger quantity of microbes can get into the bloodstream, like if a person has an obvious open wound or an abscess, during a dental or surgical procedure, or use of infected needles.
These microbes can float around in the blood for long enough to reach the heart. A particular site that’s prone to infections is the heart valve which is supplied by tiny blood vessels.
Now, most often the valves on the left side are affected, the most common being the mitral valve and the aortic valve. This is sometimes due to predisposing conditions, with the most common one in high- and middle-income countries being mitral valve prolapse and, less often, bicuspid aortic valves.
So on these valves bacterial colonies, clots and fibrin, can also form vegetations. They usually present on the mitral or aortic valve, but what’s special here is that they can present on either surface of the valve, though most commonly, on the undersurface.
Let’s now go over the microbes that can cause endocarditis. Viridans Streptococci , especially Streptococcus sanguinis, is the most common cause.

Microbiology3:50–7:44

They have low virulence, are found in the mouth, and they typically only affect valves that have had some previous damage, so think older patients or those with a history of heart valve disease after a dental procedure.
That’s because S. sanguinis uses special molecules on its surface, called dextrans, that bind to fibrin-platelet aggregates on damaged heart valves.
This usually results in small vegetations which don’t destroy the valve. Staphylococcus aureus, on the other hand, is a highly virulent bacteria that can be found on the skin, and it can infect damaged valves.
They are often introduced via surgical procedures, wounds, or intravenous drug use, and often affects the tricuspid valve.
S aureus causes large vegetations that can destroy the valves. Next we have Staphylococcus epidermidis.
A high yield fact is that this bacteria loves foreign prosthetic material, like prosthetic heart valves and this could be your best clue on a test.
This bacteria is usually introduced into the body at the time of heart valve surgery and it literally creates an extracellular matrix around itself called biofilm which allows it to stick around on the valve.
Another common point of entry into the body is through an infected intravenous catheter. Enterococcus is a part of the normal urogenital flora.
But following genitourinary catheterization or surgery, it can escape into the bloodstream and go on to cause enterococcal endocarditis on either damaged or healthy valves.
Another bacterial species is Streptococcus gallolyticus, previously known as Streptococcus bovis which is normally found in the gut flora.
But, when there’s colorectal bleeding, like with colorectal cancer, these gut bacteria can migrate across the gut lining and into the bloodstream, which can develop into endocarditis.
A high yield fact to remember is that in case of S gallolyticus endocarditis, we need to do a colonoscopy to look for colorectal cancer.
An even more unusual bacteria is Coxiella burnetii which patients typically contract after exposure to infected animals like cows, sheep, and goats.
The bacteria initially causes a disease called Q fever, but the infection could be asymptomatic. What makes this hard to diagnose is that endocarditis can develop months or sometimes years after the initial infection, but usually this is in high-risk people, like those that are immunocompromised, pregnant individuals, and those with pre-existing heart valve defect, which makes it tricky to diagnose unless there’s a reason to suspect it.
The most commonly affected valves are the mitral and aortic valves. Next, a group of organisms associated with endocarditis are the HACEK organisms, which are gram-negative bacteria that are also part of the normal flora of the mouth and throat.
Each letter of HACEK stands for a different genus; Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella.
We use to suspect them as a major cause of infective endocarditis, but recent research has shown that they are only responsible for a very small number of cases.
Finally, in really rare occasions, infective endocarditis can be caused by Pseudomonas species, or Bartonella species, both of which are gram-negative bacteria, or by fungi like Candida.
Pseudomonas and Candida endocarditis are usually associated with Intravenous drug use, in which case, the tricuspid valve is most commonly involved, while Bartonella can be transmitted by cats.
Okay, now, from a clinical point of view, infective endocarditis can be classified into groups like acute and subacute based on how quickly the infection developed.

Symptoms7:44–9:50

With acute endocarditis, the infection develops quickly and it’s most often caused by Staphylococcus aureus, while with subacute endocarditis, the infection has a gradual onset and it’s most often caused by viridans streptococci.
Now people with infective endocarditis almost always have a fever, as well as a new heart murmur, that results from turbulent blood flow past a damaged heart valve.
Sometimes those vegetations can detach from the valve to float through the bloodstream, and this is called septic emboli.
Remember that a septic emboli from the left side of the heart can lodge in the arterial circulation of the brain, causing ischemic stroke, while right-sided ones can lodge in the pulmonary circulation as pulmonary emboli.
More rarely, there might be a paradoxical embolus which dislodges from the right side, and then slips through an atrial septal defect or patent foramen ovale.
It enters the left atrium, and from there it can head off to the blood vessels supplying the brain, causing ischemic stroke.
Now, a couple of very high yield signs! Septic emboli can also get stuck under the fingernails, causing splinter hemorrhages, or in the palms and soles of the feet, causing small painless, flat, and erythematous lesions, called Janeway lesions.
The pathogens can also trigger an immune reaction where the antigen-antibody complexes that form can deposit in different parts of the body.
In the fingers and toes, these complexes can lead to painful, red, raised lesions called Osler’s nodes, in the eye these deposits can lead to Roth spots.
For your exams, remember that sometimes, these deposits can reach the kidney, leading to glomerulonephritis, in which case the individual may present with oliguria and high serum levels of BUN and creatinine.

Diagnosis9:50–10:28

Diagnosis of infective endocarditis is based on the Duke’s criteria, which take into account the clinical presentation, blood cultures for microbiologic data, and echocardiography.
For your exams, remember that finding the cause typically involves getting multiple blood cultures. Next, remember that if the blood cultures are negative, then the culprit may be one of the following: Coxiella burnetii, Bartonella, a bacteria from the HACEK group, or fungi like candida.
Echocardiography can also be used to visualize the heart and look for vegetations or more subtle clues like abnormal valve movement.
It’s also important to prevent infective endocarditis, especially among high risk groups, such as people with prosthetic heart valves or a history of endocarditis.

Prophylaxis10:28–10:52

Before dental procedures, sometimes these people are recommended antibiotics, specifically amoxicillin; remember, some of those microbes that cause endocarditis live in the mouth.
All right, as a quick recap, Endocarditis is inflammation of the endocardium which can affect the heart valves, the mural endocardium or prosthetic valves.

Review10:52–12:38

Endocarditis is usually due to a microbial infection, but in some cases can also be non-infectious. Non-infectious endocarditis is caused by damage to the endocardium which causes tiny blood clots that form vegetations on valves and this is called Nonbacterial Thrombotic Endocarditis or NBTE.
This can happen with hypercoagulable states, malignancies, or systemic lupus erythematosus. Now, in infectious endocarditis, microbes reach the bloodstream and attack the endocardium, which usually affects the valves on the left side, especially the mitral valve.
Remember, with IV drug use, the tricuspid valve is at risk. Infective endocarditis is usually caused by low-virulence viridans streptococci which attack valves that have had some previous damage.
Other causes include Staphylococcus aureus which can affect damaged valves, Staphylococcus epidermidis which affects prosthetic valves.
In Streptococcus gallolyticus endocarditis, remember to check for colon cancer. Coxiella burnetii can cause endocarditis month to years after the initial infections.
Next, Remember that HACEK, Bartonella, Candida, and Coxiella are culture negative! Clinically, individuals present with fever, splinter hemorrhages, Janeway lesion, Osler nodules, Roth spots and sometimes even glomerulonephritis.
Blood cultures, as well as echocardiography is needed for the diagnosis. Now, back to our cases.

Summary12:38–13:59

Darren came in with a fever, along with chills and fatigue. On the clinical examination, his fingernails had splinter hemorrhages and Janeway lesion.
Both of these signs are consistent with endocarditis. Now, Darren also had some track marks of his forearm.
This is consistent with IV drug use. Blood cultures showed that Darren had an infection with Staphylococcus aureus and echocardiography showed that the tricuspid valve was damaged.
So, Darren has infective endocarditis caused by S.aureus and associated with IV drug use. Then there’s Anna, who came in with a fever and the same lesion consistent with endocarditis that Darren had.
On auscultation, there was a heart murmur. Now, considering that Anna has a history of endocarditis, this means that her heart valves may be damaged.
Blood cultures showed that Anna had an infection with viridans streptococci, which makes sense, since she said that she had been to the dentist about 2 weeks ago.
Echocardiography showed tiny vegetations in the mitral valve. So Anna has infective endocarditis caused by viridans streptococci and in her case, infective endocarditis following a dental procedure.