Endocarditis

Pathogenesis

The pathogenesis of IE usually starts with an area of endocardial injury leading to platelet/fibrin deposition. Then, based on predisposing factors, when certain microorganisms enter the bloodstream, adherence occurs to the area of injury, as was demonstrated in a rabbit model of endocarditis by Durack and colleagues in 1972. Injury and infection most commonly occur on the valve leaflets but can also occur on or near congenital defects, chordae, chamber walls, prosthetic material, pacemaker leads, or any other endocardial location where favorable conditions exist. Microorganism adherence factors facilitate the initial colonization of the injured valve surface. Staphylococcus and Streptococcus species produce the majority of the human cases of IE because of their ability to adhere to damaged tissues of the heart. Conversely, Escherichia coli can be a common cause of bacteremia from urinary or gastrointestinal sources but is a rare cause of endocarditis because it lacks these adherence factors. The causes of native valve endocarditis (NVE) and their frequencies, as found by the International Collaboration on Endocarditis, are as follows: S. aureus , 31%; viridans group streptococci, 17%; coagulase-negative staphylococci, 11%; enterococci, 10%; Streptococcus gallolyticus (formerly S. bovis ), 6%; other streptococci, 6%; HACEK ∗

∗ Haemophilus parainfluenza , Aggregatibacter spp, Cardiobacterium hominis , Eikenella corrodens , Kingella spp.

, 2%; fungi/yeast, 2%; polymicrobial, 1%; other, 4%; and culture negative, 10%. The most common cause of culture-negative endocarditis is Coxiella burnetii , the etiologic agent of Q fever.

In 1978 Drs. Sheld, Valone, and Sande described the role of dextran, platelets, and fibrin in the adherence of streptococci to damaged endocardial tissue. Staphylococci use a variety of surface-bound adhesion components to bind to fibrinogen for colonization and to fibronectin for invasion. Certain coagulase-negative staphylococci such as Staphylococcus lugdunensis and Staphylococcus schleiferi possess a clumping factor that also binds fibrinogen and fibronectin as virulence factors. Enterococcus faecalis utilizes pili and collagen adhesion to facilitate adherence and aggregation. Once attached to the platelet-fibrin nidus on injured cardiac tissue, bacteria begin to multiply, increasing activation of coagulation cascade, attracting leukocytes, and grow in a further inflammation-promoting vegetation ( Fig. 36.1 ). This, in effect, buries bacteria deep within the mature vegetation, creating a biofilm environment. The unique behavior of microorganisms within this biofilm and the difficulty of antimicrobial penetration contributes to the treatment challenge of IE.

Risk Factors

Patient factors that predispose to IE are those that create damage to the valvular surface, increase the incidence of bacteremia, or slow the immune response to infection. Endocardial and valvular pathology that can be seen with congenital processes such as bicuspid aortic valves or septal defects predispose to injury. Acquired valvular damage then may occur from atherosclerotic changes and rheumatic fever. Prosthetic heart valves of any type, prosthetic material used to repair congenital heart disease, and implantable cardiac devices are considered significant risk factors. Injection drug use leads to both valvular injury and frequently introduces bacteria into the bloodstream and therefore is a synergistic risk for IE. Hemodialysis likewise creates opportunity for frequent episodes of transient bacteremia owing to regular vascular access. Increasingly, exposure to health care procedures has become recognized as a risk factor. Diabetes mellitus and other diseases leading to phagocytic cell dysfunction are predisposing factors in some cases. Men tend to be predominant in most series, with ratios ranging from 3:2 to 9:1. The elderly have nearly five times the risk of younger individuals. This is likely because of the increased prevalence of degenerative valve disease, increased use of invasive procedures, implanted medical devices, atrophy of skin, and senescence of the immune system. Children with IE almost always have underlying congenital heart disease as the main risk. In both children and adults, a previous episode of IE is a notable risk factor for a subsequent infection.

Clinical Presentation

Historically, endocarditis was a syndrome recognized by the chronic and diverse clinical findings depicted in the Netter illustrations. Now the rapid detection of bacteria with automated continuously monitored blood culture systems allow for much earlier diagnosis. Often, the first presenting sign of an eventual diagnosis of IE is a positive blood culture obtained in the evaluation of fever. Ninety-six percent of IE patients present with fever, and about 85% have an audible heart murmur, either new, worsening, or preexisting. Some patients still present with the classic manifestations of endocarditis after weeks of constitutional symptoms, depending on the virulence of the infecting organism. This subacute presentation is more common with viridans group streptococci, HACEK organisms, and Enterococcus . Endocarditis is often classified based on the acuity of the presentation and the type of valve: acute or subacute; native valve or prosthetic. The diagnosis should be suspected in any patient with risk factors, evidence of chronic inflammation (e.g., fever, chills, or night sweats) and a corresponding laboratory result of an elevated erythrocyte sedimentation rate, C-reactive protein, or rheumatoid factor with findings such as leukocytosis, anemia, and thrombocytosis. The distal physical findings of subungual splinter hemorrhages (8%), Janeway lesions (5%), Osler nodes (3%), and Roth spots (2%) occur rarely. More common clinical findings are worsening valvular dysfunction with resultant early CHF, conduction abnormalities including atrioventricular block, mycotic aneurysms, vascular embolic lesions ( Fig. 36.2 ) including embolic stroke, intracerebral hemorrhage, splenic or renal infarcts, septic pulmonary embolic from right-sided IE, petechiae of the conjunctivae, oral mucosa, or extremities, metastatic abscesses, septic arthritis, and vertebral osteomyelitis.

Diagnostic Approach

Part of the challenge of IE is that the diagnosis is usually made based on a constellation of clinical and laboratory findings without direct pathologic evidence of endocardial infection. In general, the diagnosis rests on the presence of an intravascular infection and evidence of endocardial involvement. The former is most commonly the growth of a typical organism on several blood cultures. Endocardial involvement is inferred by a new cardiac murmur, echocardiographic evidence of an endocardial vegetation, or the pathologic evaluation of a surgical specimen. Because there is no single definitive test result that is pathognomonic, syndromic diagnostic criteria have been used for many years. The first criteria were proposed in 1977 by Pelletier and Petersdorf. The most recently accepted criteria are often referred to as the “Duke criteria” and have been used in their modified state since 2000 ( Boxes 36.1 and 36.2 ). These criteria are more suited to left-sided NVE than to right-sided or prosthetic valve endocarditis (PVE) and must be utilized with significant clinical judgment, as their sensitivity and specificity for diagnosing IE are only around 80%.