Leukemia (Blood Cancer)

 Endocarditis means “inflammation of the inner layer of the heart”. The heart wall’s made up of three layers, the epicardium being the outermost layer, then the myocardium, and then the endocardium, which is the layer that gets inflamed. It turns out that most cases of Endocarditis are due to microbial infection of the endocardium. Any area of the heart that is exposed to turbulent blood flow (such as a narrowed cardiac valve or a septal defect) could be affected by Endocarditis. The turbulence of blood flow causes damage to the endocardial lining. That damage exposes the underlying collagen and tissue factor, which causes platelets and fibrin to adhere, which forms this tiny thrombosis or blood clot. This is called Nonbacterial Thrombotic Endocarditis or NBTE, and it's nonbacterial because it happens even before the bacteria shows up.

Then, a microbe has to first get into the bloodstream, and that might happen if a person has an obvious open wound or an abscess, a dental or surgical procedure, or injection with an infected needle or infected substance usually while using illicit drugs. The valves are often affected because they are often the site of turbulent blood flow. Most often the valves on the left side are affected, the mitral valve and the aortic valve, sometimes due to predisposing conditions like mitral valve prolapse and bicuspid aortic valves. Risk factors for developing Endocarditis include having prosthetic valves, having a congenital cardiac defect involving the valves, having damage to the valves from rheumatic heart disease, and finally, intravenous drug use can put valves at risk.

Although most cases of tricuspid valve Endocarditis are due to intravenous drug use, the majority of intravenous drug-using patients with Endocarditis have left-sided valvular Endocarditis. Even without using intravenous drugs, there are many opportunities for microbes to get into the bloodstream whether it’s through brushing your teeth and having them slip into the gums, or having them slip in through your gut or lungs, whatever the case they regularly make their way into the body. It’s usually not a problem though, because it’s a small amount and can easily be killed by our immune system, but occasionally they float around in the blood for long enough to find an NBTE which serves as a perfect location for them to attach to and set up an infection - called vegetation.

To attach to it a lot of bacterial species use proteins on their surface called adhesins, that let them stick to the valve as well as stick to one another. They also create an extracellular matrix around themselves - called biofilm which allows them to literally stick together and form a large clump of bacteria that can behave like a colony. Usually, these guys stick to areas of lower pressures since it’s easier to adhere. So let’s take mitral valve regurgitation, where blood flows backward from the higher pressure left ventricle to the lower pressure left atrium. So in this case, vegetations will tend to form on the lower pressure atrial surface. Not only that, though, they’ll form on the edge of the opening, and this is because of the venturi effect.

The venturi effect describes how fluid pressure decreases as it flows through a narrowed opening, while its velocity increases. So as blood forces its way through the opening, pressure is lower near the edges. If the person had aortic regurgitation, meaning blood’s going from the higher pressure aorta to the lower pressure ventricle, then vegetations would tend to be located on the lower pressure ventricular surface of the valve. Infective Endocarditis used to be classified into groups like acute and sub-acute based on how quickly the infection developed, but nowadays the key is to identify the microbial cause of infection and to treat it as effectively as possible. Viridans Streptococci is the most common cause. Its virulence is low, it’s found in the mouth, and they usually attack valves that have had some previous damage, usually resulting in small vegetations which don’t destroy the valve.

On the other hand, Staphylococcus aureus is a highly virulent bacterium found on the skin. This guy can infect both damaged and healthy valves—often the tricuspid valve. Staphylococcus aureus causes large vegetations that can destroy the valve, and is the bacteria most commonly contracted from intravenous drug use. Next, we have Staphylococcus epidermidis, which is a bacteria that loves foreign prosthetic material, like prosthetic heart valves. One way that the bacteria gets into the body is at the time of heart valve surgery and it literally sticks around on the valve. Another common point of entry into the body is through an infected intravenous catheter. Both of these scenarios usually happen in a hospital, so this would be considered a nosocomial infection.

Two other bacterial species are Enterococcus faecalis and Streptococcus bovis which are both normally found in the gut flora. But, when somebody has a severe colorectal disease, like colorectal cancer or ulcerative colitis, these gut bacteria can migrate across the gut lining and into the bloodstream, which becomes a setup for potential Endocarditis. 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 months or sometimes years after the initial Q fever, they can develop Endocarditis, but usually, this is in high-risk people, like those that are immunocompromised, pregnant women, and those with pre-existing heart valve defect, which makes it tricky to diagnose unless there’s a reason to suspect it.

Finally, a group of organisms that are less commonly associated with Endocarditis is the HACEK organisms. These guys are a group of 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. Finally, fungal Endocarditis can also occur but this happens mostly in intravenous drug-using patients or patients in the intensive care unit on multiple antibiotics. It’s important to remember fungi as routine bacterial blood cultures won’t grow them. 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, and little clumps of pathogens can float through the bloodstream—called septic emboli. These guys can lodge under the fingernails, causing splinter hemorrhages, or in the palms and soles of the feet, causing small painless, flat, and erythematous lesions, called Jane way lesions. Separately there might be an immune reaction with antigen-antibody complexes that form and deposit in different parts of the body. In the fingers and toes, these complexes can lead to painful lesions called Osler’s nodes. In the eye, these deposits can lead to Roth spots, and in the kidney, they can lead to glomerulonephritis (inflammation of the glomerulus of the nephron).

Diagnosing the cause of infective Endocarditis typically involves getting multiple positive blood cultures, which are literally growing bacteria from a blood sample. Echocardiography can also be used to visualize the heart and look for vegetations or more subtle clues like the way the valve’s moving. Depending on the organism that caused the infection, a prolonged course of antibiotics will likely be used to try and wipe out the infection but surgery might be needed for severe cases, especially when the valve dysfunction causes heart failure or there are multiple emboli. It’s also important to prevent Endocarditis, especially among high-risk groups like example those with prosthetic heart valves, a history of a heart transplant, and a history of Endocarditis.

Before dental procedures, sometimes these people are recommended antibiotics since remember that some of those microbes that cause Endocarditis live in the mouth. Finally, there’s Libman-Sacks Endocarditis, which is not infection-related. This one’s usually associated with systemic lupus erythematosus, which is an autoimmune disease involving antigen-antibody complex, and in this case, they settle in the endocardium and cause inflammation. These areas of inflammation can happen anywhere on the valve surface or chordae tendineae but typically happen on the mitral valve, leading to mitral valve regurgitation. In this case, inflammation can also happen in the atrial endocardium or ventricular endocardium.

Alright, so to recap, Endocarditis or inflammation of the endocardium typically develops from bacterial infection—usually in this case, there’s first some damage or injury to the heart valves, which leads to thrombi which serve as a place for bacteria to adhere to and cause inflammation. Sometimes, though, it can be nonbacterial, one example being Libman-sacks Endocarditis, which is associated with Lupus—an autoimmune disease.  

                Helping current and future clinicians focus to learn to retain and thrive  

Thank You