• Endocarditis = inflammation of the internal lining of the heart, called the endocardium.
• Endocarditis can be acute or subacute, depending on the presence and virulence of infective pathogens and the health of the cardiac tissue. Acute endocarditis can present with fever, chills, and other flu-like symptoms.
• Endocarditis is characterized by the formation of vegetations, which comprise micro-organisms and/or thrombotic elements. As we’ll see, some vegetations contain pathogens, such as bacteria or fungi, while others contain only thrombotic components.
  – Most vegetations are found on the valvular ring or leaflets, but they can also form on the walls of the heart; these are referred to as “mural” vegetations (aka, parietal vegetations).
  – Vegetations can ultimately invade and destroy the underlying tissues, or they can break free and become emboli.

VEGETATION FORMATION

Valvular damage

Vegetations are more likely to form where valvular damage already exists. In many cases, the initial inflammation is caused by catheter-induced abrasion or prosthetic devices.

• Endothelial damage promotes the deposition of fibronectin and vegetation formation.
  – Fibronectin adheres to circulating fibrin, platelets, white blood cells, and, if present, pathogens. Elsewhere, we’ll learn the pathogenic mechanisms of Staphylococcus aureus, a primary cause of infectious endocarditis.
• Vegetations can break free and travel within in the circulatory system.
  – They can become lodged in blood vessels and cause embolism and/or spread bacteria or fungi in the blood. Thus, endocarditis is associated with stroke, organ failure, and sepsis.

COMMON CAUSES

Three broad categories:

• Infective, which is characterized by the presence of pathogens in the vegetations; infective endocarditis is also referred to as bacterial endocarditis because bacteria are the most common culprits.
• Non-infective endocarditis is characterized by sterile vegetations; this category is also referred to as marantic or non-bacterial thrombotic endocarditis.
• Culture-negative endocarditis occurs when an infectious agent is believed to be the cause, but is not identifiable by routine laboratory blood culture procedures.

Bacterial-induced infective endocarditis

• Most commonly caused by gram-positive strains:
  – Staphylococcus aureus, followed by members of the Viridans group Streptococci, Enterococci, Coagulase-Negative Staphylococci, and other Streptococci.
• Gram-negative bacteria, including both the non-HACEK and HACEK groups are less frequent causes of endocarditis; it is thought that the gram-negative bacteria cannot adhere to endocardial cells as easily as the gram-positive bacteria are.
  – Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae

Fungal endocarditis

• Most commonly attributed to species of Candida (particularly C. albicans) and Asperigillus species.

Non-infective endocarditis

• Libman-Sacks endocarditis is the most common form of non-infective endocarditis; it associated with Systemic Lupus Erythematosus, a chronic inflammatory disease.
• Some other inflammatory conditions can also facilitate the formation of sterile vegetations.

Culture-negative endocarditis

• Some common causes of culture-negative endocarditis are the bacteria Coxiella burnetii, Brucella species, and Tropheryma whipplei.

RISK FACTORS AND PATTERNS OF ENDOCARDITIS

Turbulent blood flow promotes vegetation formation

• Mitral valve regurgitation tends to produces lesions and vegetations on the atrial leaflet surface.
• Aortic insufficiency tends to produce vegetations on the ventricular side (if you are unfamiliar with mitral and/or aortic valve dysfunction, see our tutorial on heart murmurs).
• Ventricular septal defects produce vegetations on the right side of the heart, near the orifice.

Special cases

• Intravenous drug use is a major cause of right-sided valvular endocarditis.
  – This is because particulate matter within the syringe, such as talc, or surface pathogens on the skin can be introduced into the blood stream during injection (in addition, the use of saliva on injection needles can introduce oral bacterial flora into the blood).
• Prosthetic valves are more susceptible to infection because bacteria and debris adhere to prosthetic materials.
  – Furthermore, the surgery and/or healing process itself creates a vulnerable environment; Staphylococcus aureus and Coagulase-negative Staphylococcus are common culprits.
  – For example, invasive vegetations can form where the prosthetic annular ring meets the valvular tissue; inflammation can easily lead to the formation of bacterial vegetations that ultimately deform the valvular leaflets. In many cases, surgery is required to replace the valve.
• Rheumatic heart disease can produce valvular vegetations that are small and tend to be located near the edge of the leaflet.
• Libman-Sacks endocarditis, which, as we mentioned earlier, is associated with Systemic Lupus Erythrmatosus, presents with small and medium-sized vegetations on both sides of the leaflets. As a type of non-infective endocarditis, there less inflammation, and, therefore, the vegetations are loosely attached.
  – Thus, the risk of embolism is increased in patients with non-infective endocarditis.