Pathophysiology of infective endocarditis

Sequence of events

1. Endothelial injury or a susceptible surface
   • Normal intact endocardium resists infection.
   • Turbulent, high-velocity blood flow causes microscopic endothelial damage, especially with abnormal valves, congenital heart disease, prosthetic valves, intracardiac devices, or previous IE.
   • Injury exposes collagen and tissue factor.
2. Formation of sterile platelet-fibrin thrombus
   • Platelets and fibrin deposit at the injured site, forming a small sterile lesion called nonbacterial thrombotic endocarditis.
   • Typical sites are on the low-pressure side of a valve leaflet, where turbulent jets strike the endocardium.
3. Transient or persistent bacteremia
   • Organisms enter the circulation from skin infection, intravenous catheters, injection drug use, dental/oral sources, gastrointestinal or genitourinary procedures, or invasive infections elsewhere.
   • Common pathogens include Staphylococcus aureus, viridans streptococci, enterococci, and coagulase-negative staphylococci in prosthetic-device infection.
4. Adherence and colonization
   • Microbes adhere to the platelet-fibrin nidus through microbial surface adhesins that bind matrix proteins such as fibronectin, fibrinogen, and collagen.
   • S. aureus is highly virulent and may infect even apparently normal native valves.
   • Bacteria multiply within the thrombus and provoke more platelet activation and fibrin deposition.
5. Vegetation growth and biofilm formation
   • The vegetation enlarges into an avascular, dense, infected mass.
   • Organisms are shielded by fibrin, platelets, and, particularly on prosthetic material, biofilm. This limits penetration by neutrophils, antibodies, complement, and antibiotics.
   • The result is persistent bacteremia and relative resistance to antimicrobial therapy. This sequence is described in Fuster and Hurst's The Heart, pp. 1024-1025.

Consequences of vegetations

Important clinical correlations

• Left-sided IE usually affects the mitral or aortic valve and causes systemic arterial emboli.
• Right-sided IE, often tricuspid in people who inject drugs or those with intravascular catheters, causes pulmonary septic emboli.
• Prosthetic-valve and device-associated IE is especially difficult to eradicate because biofilm enables persistent infection.
• The local destructive effects can cause acute severe mitral or aortic regurgitation, abscess formation, and heart block. The Merck Manual overview summarizes these local and systemic complications.