- Blood cultures positive for bacteria or fungi.
- Cardiac lesions on echocardiography.
Infective endocarditis is one of several infections in which endothelium is the initial site of infection. Healthy endothelium possesses
an effective system of defense against both hemostasis and infection. Infection of the endothelium of blood vessels occurs only at sites markedly altered by disease or surgery, such as the severely atherosclerotic aorta or the suture lines of vascular grafts. By contrast, infection
of the cardiac valve leaflet endothelium (endocardium) is not rare and occurs even in the absence of identifiable preexisting valve disease.
Precursor Lesion and Bacteremia
Valve infection probably begins when minor trauma, with or without accompanying valve disease, impairs the antihemostatic function
of valve endocardium. Infection usually first appears along the
coapting surface of the leaflets, suggesting a role for valve opening
and closing. This hypothesis is supported by the observation that the
ranking of valves in order of frequency of infection corresponds
to the ranking of valves according to the force acting to close
the valve (mitral > aortic > tricuspid > pulmonic).
This minor trauma may cause the formation of a microscopic thrombus on the leaflet surface. A small noninfected thrombus on the leaflet is called nonbacterial thrombotic endocarditis (NBTE). The
next step is infection of the fibrin matrix of the thrombus by blood-borne organisms,
which appear briefly in blood under many circumstances, such as brushing
one’s teeth. When transient bacteremia coincides with the
presence of an NBTE lesion, organisms may adhere to the valve leaflet
and begin to proliferate.
This theory for the pathogenesis of endocarditis is supported by observations regarding the circumstances under which endocarditis
occurs and the particular organisms involved. Patients with endocarditis often tell of a preceding event that likely resulted in transient bacteremia. The common infecting organisms are those that gain entry to the blood because they colonize body surfaces and are adapted for attachment and proliferation in the NBTE lesion (see Clinical Syndromes).
Vegetations begin near the coaptation line of the leaflet on the side that contacts the opposite leaflet during valve closure. Mitral
valve vegetations are typically attached within 1–2 cm of the leaflet tip on the left atrial side and prolapse into the left atrium during systole. Aortic valve vegetations usually occur on
the left ventricular (LV) side of the mid- or distal portions of the aortic cusps and prolapse into the LV outflow tract during diastole. A similar distribution of lesions occurs on the tricuspid and pulmonic
Although the course of cardiac lesions in endocarditis varies, in a typical sequence of events (without treatment), the infection
progresses by enlargement of the vegetation and extension of its
region of attachment toward the base of the leaflet. Valve regurgitation
almost always develops, as a result of either destruction of the
leaflet tip or scarring and retraction of the leaflet. Erosion of
the leaflet may lead to perforation (usually associated with clinically
significant regurgitation). Weakening of the leaflet’s
spongiosum layer may result in a deformity called a leaflet aneurysm.
Mitral or tricuspid chordal involvement may cause rupture and acute
severe regurgitation. In rare cases (primarily in mitral bioprosthetic endocarditis;
see Management of High-Risk Endocarditis), a large vegetation may cause hemodynamically significant valve obstruction.
These vegetations may form when the regurgitant jet of blood from an infected valve strikes an endocardial surface in the receiving chamber
(wall or chordae), producing a small area of denuded endothelium.
The thrombus that forms at this site also becomes infected, constituting
a secondary vegetation. Such metastatic vegetations most often appear
on the ventricular side of the anterior mitral leaflet where it
is struck by a regurgitant jet from aortic valve endocarditis. Another common
location is on the mitral chordae, also from aortic regurgitation. Metastatic
lesions on the mural endocardium of the cardiac chambers can occur as
Abscess and Fistula Formation
Organisms eventually invade the valve annulus and adjacent myocardium. Abscess formation can take multiple forms and may occur with or without fistula formation. Aortic annular abscess is an infective mass that
burrows into or around the outside of the annulus. The abscess may
extend upward to the sinus of Valsalva or ascending aorta (a type
of mycotic aneurysm). This extension may lead to a fistulous communication between
the aorta and the left atrium or (rarely) the right atrium. In other
patients, the abscess extends down through the fibrous trigone and
forms a fistula to the LV outflow tract.
A band of fibrous tissue at the base of the anterior mitral leaflet (the intervalvular fibrosa) separates the aortic annulus from the
left atrial wall. Infection extending down from the posterior aortic
annulus may produce an aneurysm in this area, which may in turn
fistulize to the left atrium, aortic root, or into the pericardial space.
Infection extending down from the anterior aortic annulus may invade
the septal myocardium, causing a block in the conduction system.
When mitral valve infection extends to the base of the anterior leaflet, abscess formation involving the fibrous trigone may track
upward and become fistulous. Infection from the posterior leaflet
may extend to form a myocardial abscess in the LV posterior wall
or a fistula around or through the mitral annulus between the left
atrium and left ventricle. Infection may even penetrate through
to the pericardial space, producing purulent pericarditis.
At any time during cardiac infection, extracardiac complications may supervene and dominate the clinical picture. Although these
manifestations are emphasized in the medical literature, it should
be kept in mind that many patients with endocarditis do not have
them, especially at the time of presentation. The extracardiac disease
in endocarditis ...