Vegetation formation is a multistep process. The first step is endocardial injury, which may occur by many mechanisms. The most common mechanism is injury by turbulent blood flow from an acquired or congenital intracardiac abnormality. The most common site of such injury, and thus the most common site of vegetation formation, is on the line of closure of a valve surface, typically on the atrial surface of atrioventricular valves, or the ventricular surface of semilunar valves [2
]. Alternatively, an intravascular catheter or other device may directly abrade the endocardium. In injection drug users, direct injection of contaminating debris may damage the tricuspid valve surface.
The endothelial damage triggers sterile thrombus formation, which occurs by deposition of fibrin and platelets. Though mechanical endocardial damage usually precedes sterile thrombus formation, a sterile thrombus can be induced without direct trauma [3
]. Physiologic stresses such as hypersensitivity states, hormonal changes, and high altitude can also induce sterile endocardial thrombosis [3
]. Clinical states associated with sterile thrombus formation in humans include malignancy, rheumatic diseases, and uremia.
Once a sterile thrombus is present, transient bacteremia can seed the thrombus. Bacteria are introduced into the bloodstream when a body surface that is heavily colonized by bacteria (oral cavity, gut lumen, genitourinary mucosa) is traumatized. Routine daily activities such as chewing food and tooth brushing lead to frequent low-level, transient bacteremias in healthy adults [4
]. Bloodborne bacteria may adhere to the damaged endocardial surface. Bacteria have different adhesive capacity, based on bacterial surface characteristics and virulence factors called adhesins. For example, the adhesive properties of viridans streptococci are related the amount of dextran present in the streptococcal cell wall, as well as specific surface proteins such as FimA [5
Once bacteria have attached to the endocardium, the vegetation “matures” through additional deposition of fibrin and bacterial proliferation. Histologically, the vegetation consists primarily of fibrin, platelets, and bacteria; the absence of vasculature makes penetration by phagocytic cells rare. The majority of bacteria in a mature vegetation are found below the surface of the vegetation, protected from phagocytes and high concentrations of antibiotics.