Pathogenesis of Vegetation Formation in Infective Endocarditis
Pathogenesis of Vegetation Formation in Infective Endocarditis
Pathogenesis of Vegetation Formation in Infective Endocarditis
Author
Daniel J Sexton, MD
Section Editor
Stephen B Calderwood, MD
Deputy Editor
Elinor L Baron, MD, DTMH
Disclosures: Daniel J Sexton, MD Grant/Research/Clinical Trail Support: Cubist [C. difficile infection
(Fidaxomycin)]. Consultant/Advisory Boards: Johnson & Johnson [Pelvic mesh-related infection]; Sterilis [Medical
waste disposal systems]; Magnolia Medical Technologies [Intravenous devices]. Other Financial Interest:
National Football League [Infection control program]. Equity Ownership/Stock Options: Magnolia Medical
Technologies [Intravenous devices]. Stephen B Calderwood, MD Patent Holder: Vaccine Technologies Inc.
[Vaccines (Cholera vaccines)]. Equity Ownership/Stock Options: Pulmatrix [Inhaled antimicrobials]; PharmAthene
[Anthrax (Anti-protective antigen monoclonal antibody)]. Elinor L Baron, MD, DTMH Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
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Literature review current through: Mar 2015. | This topic last updated: Jan 10, 2014.
INTRODUCTION Infective endocarditis arises when an adherent platelet-fibrin nidus
becomes secondarily infected and produces vegetations, which in turn may directly damage the
endocardial tissue and/or valves. The pathogenesis of infective endocarditis will be reviewed
here.
Other aspects of infective endocarditis, including clinical consequences of vegetation formation,
are discussed separately. (See "Epidemiology, risk factors and microbiology of infective
endocarditis" and "Epidemiology, clinical manifestations, and diagnosis of prosthetic valve
endocarditis" and "Infective endocarditis in injection drug users" and "Infective endocarditis in
children" and "Clinical manifestations and diagnosis of infective endocarditis" and"Antimicrobial
therapy of native valve endocarditis" and "Antimicrobial therapy of prosthetic valve
endocarditis" and "Surgery for native valve endocarditis"and "Complications and outcome of
infective endocarditis".)
PATHOGENESIS
Vegetation formation The endothelial lining of the heart and its valves is normally resistant
to infection with bacteria and fungi. Experiments in animal models have demonstrated that a
sequence of interrelated events must occur before microbes can establish an infective nidus or
vegetation on the endocardium:
The initial step in the establishment of a vegetation is endocardial injury, followed by
focal adherence of platelets and fibrin. Some organisms with high virulence are capable of
infecting normal human heart valves, such as Staphylococcus aureus.
The initially sterile platelet-fibrin nidus becomes secondarily infected by microorganisms
circulating in the blood, either from a distant source of focal infection, or as a result of
transient bacteremia from a mucosal or skin source [1,2].
It is likely that the pathogenesis of vegetation formation varies depending on the infecting
organism. In most instances, colonization of the platelet-fibrin aggregate is an initial event.
Subsequent microbial growth results in further activation of the coagulation system via the
Vegetation sites Vegetations tend to develop at sites where blood travels from an area of
high pressure through a narrow orifice into an area of lower pressure. The explanation for this
phenomenon can be deduced from in vitro experiments demonstrating the physics of turbulent
flow. As an example, it has been observed that, following injection of nebulized bacteria into an
air stream passing through an agar-coated tube, the highest concentration of bacteria is found
in the low pressure area immediately distal to the narrowing [7]. The propensity for vegetations
to form at specific sites may be correlated with a decrease in lateral pressure downstream from
the regurgitant flow, which causes a decrease in the perfusion of the intimal lining at these sites
[8]:
In the setting of preexisting valvular disease, vegetations are usually located on the atrial
surface of incompetent atrioventricular valves or the ventricular surface of incompetent
semilunar valves.
In the setting of ventricular septal defect, vegetations tend to develop on the orifice of the
defect, on the right ventricular side of the opening, and/orsecondarily on the tricuspid and
pulmonic valves [9].
In the setting of aortic insufficiency, vegetations may localize to the chordae tendineae of
the anterior leaflet of the mitral valve
In the setting of mitral regurgitation, vegetations may develop on the wall of the left
atrium, where the regurgitant jet strikes the atrial wall and results in endocardial thickening
(MacCallum's patch).
Pathogen factors
Source of infection The bacterial source for endocarditis may be readily discernible (such
as a dental abscess, infected skin lesion, or infected vascular catheter), or there may be no
clear history of antecedent infection. In such cases, the source is frequently attributed to minor
trauma of the oropharyngeal, gastrointestinal, or genitourinary mucosa.
Endocarditis in injection drug users is presumed to be a consequence of bacterial contamination
of material injected, of injection equipment, and/or of the skin surface at the injection site.
Microbial adherence Microbial adherence is a crucial event in the pathogenesis of
endocarditis. Organisms typically associated with endocarditis have the capacity to adhere
avidly to valve tissue; these include S. aureus, viridans streptococci, enterococci,
and Pseudomonas aeruginosa [10]. Bacterial adherence to a platelet-fibrin nidus involves a
complex interaction of microbial cell wall components. The mechanism of adherence is poorly
understood and may vary among different organisms.
In vitro models have provided some data regarding the pathogenesis of adherence:
The relative frequency with which different species of bacteria cause endocarditis in
humans has been correlated with their ability to cause endocarditis in rabbits [8]. In this
experimental model, the amount of dextran produced by the cell wall of streptococci grown
in broth is proportional to the intrinsic ability of various streptococcus species to cause
endocarditis, suggesting the importance of the interaction between dextran and the
valvular endothelium [11].
Intrinsic binding affinity to fibronectin appears to be a contributing pathogenic factor; in
rats, S. aureus mutants with diminished capacity to bind fibronectin had reduced ability to
cause endocarditis compared with parent strains with higher fibronectin binding affinity [12].